Articles https://doi.org/10.1038/s42255-019-0109-9

Spatial sorting enables comprehensive characterization of liver zonation

Shani Ben-Moshe1,3, Yonatan Shapira1,3, Andreas E. Moor 1,2, Rita Manco1, Tamar Veg1, Keren Bahar Halpern1 and Shalev Itzkovitz 1*

The mammalian liver is composed of repeating hexagonal units termed lobules. Spatially resolved single-cell transcriptomics has revealed that about half of hepatocyte genes are differentially expressed across the lobule, yet technical limitations have impeded reconstructing similar global spatial maps of other hepatocyte features. Here, we show how zonated surface markers can be used to sort hepatocytes from defined lobule zones with high spatial resolution. We apply transcriptomics, microRNA (miRNA) array measurements and mass spectrometry proteomics to reconstruct spatial atlases of multiple zon- ated features. We demonstrate that protein zonation largely overlaps with messenger RNA zonation, with the periportal HNF4α as an exception. We identify zonation of miRNAs, such as miR-122, and inverse zonation of miRNAs and their hepa- tocyte target genes, highlighting potential regulation of gene expression levels through zonated mRNA degradation. Among the targets, we find the pericentral Wingless-related integration site (Wnt) receptors Fzd7 and Fzd8 and the periportal Wnt inhibitors Tcf7l1 and Ctnnbip1. Our approach facilitates reconstructing spatial atlases of multiple cellular features in the liver and other structured tissues.

he mammalian liver is a structured organ, consisting of measurements would broaden our understanding of the regulation repeating hexagonally shaped units termed ‘lobules’ (Fig. 1a). of liver zonation and could be used to model liver metabolic func- In mice, each lobule consists of around 9–12 concentric lay- tion more precisely. T 1 ers of hepatocytes . Blood flowing from portal nodes at the corner In this study, we developed an approach termed ‘spatial sorting’, of the lobules towards draining central veins generates gradients which uses surface markers with discordant zonation profiles to isolate of oxygen, nutrients and hormones along the lobule radial axis. very large amounts of hepatocytes from defined lobule layers (Fig. 1b). Additionally, Wnt morphogens are secreted by endothelial cells We used these for high-throughput profiling of mRNAs, miRNAs surrounding the central veins, resulting in a graded morphoge- and proteins (Fig. 1c), revealing previously unknown features of liver netic field2. This graded microenvironment gives rise to spatial zonation. These include a comprehensive proteomic zonation map heterogeneity in gene expression among hepatocytes residing and the identification of zonated miRNA with discordantly zonated at different lobule layers, a phenomenon that has been termed target genes. Our approach can be readily applied to profile other cel- ‘liver zonation’3,4,5,6. lular features of hepatocytes and other cell types in health and disease. We have recently used spatially resolved single-cell transcrip- tomics to uncover the global zonation patterns of hepatocyte gene Results expression7. We found that around half of all genes expressed in Spatial sorting enables isolating bulk hepatocyte populations hepatocytes are zonated, with specific functional specialization that from different lobule layers. We used our recently reconstructed seems to match the zonated microenvironment. This global zona- mRNA zonation map7 to identify zonated surface markers with a tion suggests that similar spatial heterogeneity of hepatocytes may large dynamic range in expression, spanning several radial lobule also exist for other cellular features, including proteins, metabolites layers (Fig. 1a and Supplementary Fig. 1a). We argued that the com- and regulatory molecules such as miRNAs. However, achieving bined staining of two inversely zonated surface proteins would be similar global zonation maps for cellular features beyond mRNA informative for inferring the lobule positions of single hepatocytes has encountered technical difficulties. (Fig. 1b), which would facilitate cell sorting of many cells according Immunohistochemistry enables the measurement of protein lev- to their spatial origin (Fig. 1b,c). CD73, encoded by the gene Nt5e, els with high spatial resolution but it is low-throughput and often is an enzyme that converts mononucleotides to nucleosides and limited by lack of availability of antibodies. Laser capture microdis- exhibits pericentral zonation7. E-cadherin, a cell–cell adhesion gly- section and digitonin perfusion enable extracting large numbers of coprotein encoded by Cdh1, exhibits periportal zonation12 (Fig. 2a). periportally or pericentrally enriched cells8,9. However, these tech- We used immunofluorescence to validate the zonation of these two niques are limited in spatial resolution. Single-cell measurements of surface markers at the protein level (Fig. 2b,c). cellular features beyond mRNA are starting to emerge10,11; however, We perfused the livers of five mice fed ad libitum to dissoci- these technologies are less mature in tissues. A methodology that ate single cells and performed fluorescence-activated cell sorting enables massive isolation of pure cell types from defined layers with (FACS) of isolated hepatocytes stained with antibodies against CD73 high spatial resolution would enable generating organ-wide spa- labelled with allophycocyanin (APC) and E-cadherin labelled with tial atlases of key features, such as methylation patterns, chromatin phycoerythrin (PE). We filtered hepatocytes by size and selected conformations, miRNA content and proteomics. In the liver, such cells that were negative for the endothelial cell marker CD31 and

1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. 2Present address: Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland. 3These authors contributed equally: Shani Ben-Moshe, Yonatan Shapira. *e-mail: [email protected]

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a b c Spatial sorting

Liver lobule

Pericentral Spatial omics FACS gates miR1 miR2 miR3

Portal node Portal node Mid-lobule Periportal AAA FACS gates FACS gates AAA AAA Central vein Central vein Pericentral surface marker

Pericentral Periportal Periportal surface marker mRNA Mass miR surface marker surface marker sequencing spectrometry microarray

Fig. 1 | Spatial sorting approach for isolating large amounts of hepatocytes from distinct layers with high resolution. a, Identification of zonated surface markers. b, FACS enables defining gates that enrich for zonated hepatocytes according to their surface marker expression. c, Spatially sorted hepatocytes can be measured using multiple assays that require large input material, such as the RNA-seq, mass spectrometry and miRNA microarray applied in the current study.

a mRNA b CD73/E-cadherin/DAPI Nt5e Cdh1 1 Central vein 2 3 Portal 0.6 1 node

mRNA expressio n 0.2 (normalized to maximum) Central Portal vein node

c Protein CD73 1 - Pericentral 2 - Mid-lobule 3 - Periportal 1 E-cadherin

0.6

0.2 Protein intensity (normalized to maximum) Central Portal vein node Lobule layer

Fig. 2 | CD73 and E-cadherin are inversely zonated surface markers. a, CD73, encoded by Nt5e, and E-cadherin, encoded by Cdh1, are surface markers that are zonated at the mRNA level (data taken from Halpern et al.7). n = 1,415 cells from 3 mice. The lines show the sum-normalized mean of all cells; the shaded regions are ±s.e.m. b, CD73 and E-cadherin proteins are zonated. An example of a lobule stained by immunofluorescence with antibodies against CD73 (red) and E-cadherin (green) is shown. Blue, DAPI nuclear stain. Scale bar, 10 µm. The experiment was performed independently on three different mice. c, Quantification of immunofluorescence images (n = 8 lobules from three mice). The lines represent the mean intensity measured in the lobule layer; the shaded regions are ±s.e.m. across the eight lobules. the immune cell marker CD45, to avoid pairs of hepatocytes and hepatocytes from each gate. Contamination of NPC RNA was neg- non-parenchymal cells (NPCs)13. We further filtered out non-viable ligible and uniform across all eight isolated populations, validating cells and selected tetraploid hepatocytes using Hoechst staining our isolation and sorting approach (Supplementary Table 1). We (Fig. 3a and Supplementary Fig. 1b). Stratifying hepatocytes by compared the zonation profiles obtained via spatial sorting to our ploidy was important to obtain precise lobule localization spatially resolved single-cell RNA-seq map7. Zonation profiles were (Supplementary Fig. 1c,d). The selected hepatocytes displayed highly concordant (Fig. 3c and Supplementary Table 2), demon- strong anti-correlation in the fluorescence of CD73 and E-cadherin, strating the feasibility of our approach for isolating bulk hepatocytes as expected from the zonated expression patterns (Fig. 3b). with high spatial resolution. We defined eight gates based on the combined fluorescence of CD73 and E-cadherin (Fig. 3b). To ensure reproducibility, the Mass spectrometry proteomic measurements of spatially sorted gates were defined as the percentiles of the marginal expression lev- hepatocytes. We next applied spatial sorting to reconstruct the els of each surface marker, compared to the unstained control. To zonation patterns of the hepatocyte proteome. To this end, we validate that our defined gates represented sequential lobule layers, sorted 100,000 hepatocytes from each of the eight FACS gates and we performed bulk RNA-sequencing (RNA-seq) on 10,000 sorted performed mass spectrometry proteomics. For each mouse and

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a c Glul Gulo 250 Hepatocyte size 105 Viability 1 1

4 0.6 0.6 10 150 0.2 0.2 3 10 12345678 12345678 SSC-A (K) Zombie Green-

50 Alexa Fluor 488-A 0 Lect2 Cyp2e1 3 –10 1 1 10 70 130 10 70 130 0.6 0.6 FSC-A (K) FSC-A (K) 0.2 0.2 105 NPC depletion Ploidy 60 K 12345678 12345678 Gsta3 Hamp 8n 1 40 K 4n 103 1

Count 0.6 0.6 20 K CD31-PE-Cy7-A 2n 0.2 0.2 101 12345678 12345678

101 103 105 103 104 105 Hamp2 Hpx CD45-APC-Cy7 Hoechst/Indo-1 1.4 1 1 b 0.6 0.6 0.2 0.2 104 RNA expression (normalized to maximum) 12345678 12345678 Alb Cyp2f2 1 1 1 0.6 0.6 2 0.2 0.2 3 12345678 12345678 3 10 Hsd17b13 Sds 4 1 1 Anti-CD73-APC (pericentral)

0.6 0.6

0 0.2 0.2

5678 12345678 12345678 Central Portal Central Portal vein node vein node 0 103 104 FACS gate Anti-E-cadherin-PE (periportal) Single-cell RNA-Seq interpolated layers 7 RNA-Seq of FACS-gated populations

Fig. 3 | Spatial sorting reliably captures the different lobule layers. a, FACS gating strategy. FSC-A and SSC-A were used for size selection of hepatocytes. Non-viable cells were filtered out using the Zombie Green Viability Kit. Staining with antibodies to CD31 and CD45 enabled the gating out of NPCs. Tetraploid hepatocytes were selected based on Hoechst staining. b, Distribution of the included cells (40–60% from all events) according to the intensities of CD73 and E-cadherin. The grey lines mark the unstained control limits; the rectangles and numbers mark the gates used for spatially sorted populations. The distributions from five independent mice were similar. c, Maximal level-normalized expression patterns of selected genes along the different FACS gates (blue, n = 5 mice), compared with the interpolated maximal level-normalized zonation profiles based on Halpern et al.7 (yellow). The lines are the mean of each FACS gate for 5 mice (blue) and the mean of each interpolated layer for the 1,415 cell from 3 mice (yellow). The line patches represent the s.e.m. gate we also isolated 10,000 cells and applied bulk RNA-seq. The hepatocyte mRNA (0.050 ± 0.004 of cellular transcripts) but was mass spectrometry measurements yielded 3,210 identified proteins ranked only 64 in protein levels (0.0034 ± 0.0002 of cellular pro- (Supplementary Table 3). The hepatocyte protein content averaged teins). Other secreted proteins, which were ranked substantially over all FACS gates was highly correlated with previous bulk mea- higher in mRNA compared to the protein level, included apolipo- surements14 (Spearman’s r = 0.75; Supplementary Fig. 2a). Our data- proteins encoded by Apoa1, Apoa2, Apoe, α-antitrypsin encoded by set included 3,051 proteins with matched mRNA (Supplementary Serpin genes, complement system proteins and vitronectin, encoded Table 4). The means over all gates of protein and mRNA levels were by Vtn (Fig. 4a). A similar discordance between the levels of mRNA positively correlated (Spearman’s r = 0.5, P = 1.2 × 10−181, n = 3,051). and proteins for secreted genes was previously observed in mam- Yet, for some proteins, there was a marked difference in protein and malian cell lines15. Ribosomal mRNA and proteins had a protein- mRNA relative abundances (Fig. 4). These predominantly included to-mRNA ratio close to 1, whereas genes of the tricarboxylic acid proteins secreted by hepatocytes. For example, Alb, which encodes cycle had substantially higher protein-to-mRNA levels (Fig. 4b the secreted carrier protein albumin, was the most highly abundant and Supplementary Fig. 2b). Cps1, which encodes the urea cycle

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a mRNA Protein

Flcn Ncoa4 Dapk1 Dapk2 Dapk3 Jup Traf4 Prcc Ccnt2 Bcl6 Bmp2k Zeb1 Nae1 Ptch1 Bmp4 Egln3 Tfrc Slc2a1 Cul2 Phkg2 Avpr1a Usp7 Prkab1 Prkag2 Smad4 Ctf1 Il13ra1 Gnaq Tr im25 Icam1 Pias4 Ticam1 Tbl1xr1 Ncstn Dtx4 Numb Neo1 Cxcl16 Flt3l Cox10 Tamm41 Wdr3 Wdr36 Nvl Lsg1 Csnk2a2 Nxt1 Nxt2 Rexo1 Nob1 Bms1 Rpp30 Mrpl50 Mrpl49 Cstf3 Smg6 Ppp2r3a Ppp2r3c Rnmt Smg1 Cpsf1 Smg5 Mlh1 Neil1 ApexUn2g Hist1h2ap Rad17 Mms19 Hus1 Smek2 Dclre1a Terf2 Terf1 Gins4 GmnnTep1 Cyp2c68 Clic4 Cd47Dag1 Cdh2 Glg1 Tfrc Cul2 Sgk2 Prkaa2 Prkag1 Stim1 Mylk Itpr2 Rapgef4 Cdh1 Icam1 Trim25 Mtor Cacybp Ncstn Dtx3l Numb Nup155 Rangap1 Eif2b2 Nup98 Pnn Dnlz Coa6 Sbds Csnk2a1 Nxf1 Nudt21 Cstf1 Mrpl39 Mrpl37 Mrpl38 Mrpl50 Mrpl49 Mrpl54 Mrpl55 Parp1 Apex1 Flcn Ncoa4 Dapk1 Dapk2 Dapk3 Traf4 Prcc Ccnt2 Bcl6 Bmp2k Pdcd4 Zeb1 Ssb Nae1 Ptch1 Bmp4 Egln3 Slc2a1Crebbp Cul2 Itpr2 Phkg2 Avpr1a Prkab1 Foxo1 Prkag2 Smad4 Ctf1 Il13ra1 Gnaq Tr im25 Icam1 Pias4 Ticam1 Tbl1xr1 Ncstn Aph1a Dtx4 Numb Neo1 Il18 Cxcl16 Flt3l Cox10 Tamm41 Wdr3 Wdr36 Dkc1 Csnk2a2 Nxt2 Nob1 Bms1 Rpp30 Cstf3 Smg6 Ppp2r3a Ppp2r3c Rnmt Smg1 Cpsf1 Cpsf3 Smg5 Mlh1 Neil1 Ung Hist1h2ap Rad17 Tceb3 Cry1Mms19Alkbh2Hus1 Smek2 Dclre1a Terf2 Terf1 Orc2GmnnTep1 Cyp2c68 Clic4 Cd47Dag1 Cdh2 Tfrc Cul2 Sgk2 Prkaa2 Prkag1 Stim1 Mylk Rapgef4 Cdh1 Gnas Icam1 Trim25 Mtor Ncstn Dtx3l Numb Nup155 Rangap1 Eif2b2 Nup98 Pnn Dnlz Rexo2 Nxf1 Eif6 Nudt21 Cstf1 Cpsf6 Mrpl38 Mrpl50 Mrpl49 Mrpl54 Mrpl55 Parp1 Apex1 Appl1 Jup Mllt1 Pdcd4 Ssb Tfrc Crebbp Itpr2 Atp2b1 Usp7 Foxo1 Aph1a Dtx3l Rfng Il18 Tbl3 Dkc1 Nvl Taf9 Lsg1 Nxt1 Rexo1 Mrpl39 Mrpl50 Mrpl49 Ppp1cb Cpsf3 Nudt21 Apex2 Hist2h2ac Tceb3 Cry1 Alkbh2 Wrn Gins4 Orc2 Glg1 Bnip3 Itpr2 Phkg2 Gnas Cacybp Sec13 Coa6 Sbds Csnk2a1 Eif6 Cpsf6 Mrpl39 Mrpl37 Appl1 Mllt1 Dicer1 Tbl1x Dtx3l Rfng Glg1 Tbl3 Hist2h2ac Wrn Bnip3 Nup210 Rexo2 Cul3 Ccdc6 Klf3 Atp2b1 Ddit4 Prkag1 Pard3 Tbl1x Glg1 Taf9 Mdn1 Mrpl39 Wdr82 Ppp1cb Nudt21 Cpsf2 Apex1 Ube2v1 Phkb Phkg2 Eif4b Nup210 Sec13 Mrpl47 Tceb1 Klf3 Dicer1 Ddit4 Pard3 Irak4 Coa7 Mdn1 Ppp2r5d Cpsf2 Ube2v1 Orc5 Phkb Ddx58 Eif1 Tceb1 Cul3 Hnf4a Ccdc6 Csnk1g2 Prkag1 Il15ra Irak4 Il1rap Dnlz Coa7 Csnk2aCsnk2a11 Rpp25l MrMrps18ps18aa Wdr82 Ppp2r5d Ppp2r2d Polb Apex1 Smek1 Pls3 Orc5 Itgb1 Gnai3 Ddx58 Ndufa3 Eif4b Ranbp2 Eif1 Eif3h Mrpl48 Mrpl47 Hnf4a Csnk1g2 Il15ra Tradd Ptprf Il1rap Dnlz Rpp25l Ppp2r2d Msh3 Polb Cry2 Smek1 Ppp4c Pls3 Terf2ip Itgb1 Gnai3 Erc1 Ndufa3 Ranbp2 Eif3h Acin1 Mrpl48 Cycs Rbpj Ccl25 Msh3 Cry2 Dkc1 Gpc1 Ppp4c Kpnb1 Bcr Egln2 Crlf2 Tradd Ptprf Terf2ip Tnks2 Gna11 Tln1 Erc1 Nup153 Acin1 Ube2k Pdk1 Cycs Rbpj Ccl25 Cox14 Asgr2 Pdk1 Ruvbl1 Upf1 Dkc1 Ppp2r1a Mrpl11 Mrps18c Gpc1 Ccl9 Kpnb1 Bcr Egln2 Bnip3 Crlf2 Tnks2 Gna11 Tln1 Nup153 Ube2k Nudt16l1 Pdk1 Cox14 Nat10 Asgr2 Pdk1 Ruvbl1 Upf1 Fbll1 Ppp2r1a Rps24 Mrpl11 Mrps18c Ss18 Bnip3 Ccl9 Tpr Rbm8a Aff1 Nudt16l1 Ethe1 Nat10 Rpp40 Eif6 Mrpl48 Pcf11 Mlh3 Cldn3 Mrpl9 Utp14a Cyp3a25 Fbll1 Rps24 Ss18 Prkaa2 Gnl2 Cyp7b1 Tpr Rbm8a Rps29 Mrps17 Aff1 Sgk2 Mrpl48 Ube2v2 Tnks Gins1 Cldn3 Ppif Gnai2 Pcf11 Mlh3 H2afy Ethe1 Rpp40 Ncor2 Eif6 Mrpl9 Fn1 Prkaa2 Cir1 Emg1 Utp14a Nudt1 Cyp3a25 Cyp7b1 Mrps17 S1pr1 Gnl2 Paip1 Nup133 Poldip2 Rps29 Sgk2 Asgr2 Nthl1 Gins1 Itga1 Gnai2 Sbds H2afy Ube2v2 Tnks Ppif Timm13 Lbp Ncor2 Ppp2r2a Eif2b4 Rara Fn1 Tlr2 Tirap Cir1 Emg1 Nudt1 Cyp2c37 Itga1 S1pr1 Sdc1 Asgr2 Coa6 Sbds Nthl1 Paip1 Nup133 Poldip2 Timm13 Rps28 Lbp Ppp2r2a Ppp4r2 Map2k1 Eif2b4 Rara Tlr2 Tirap Poldip2 Coa6 Riok1 Cyp2c37 Alcam Cab39 Nedd4 Stat6 Lrp6 Sdc1 Ppp4r1 Rps28 Nrxn3 Riok1 Ppp2r1a Ppp4r2 Ppp6r3 Alcam Cadm1 Ctnnb1 Map2k1 Cab39 Eif2b3 Nedd4 Stat6 Lrp6 Sdc2 Poldip2 Ppm1a Ldb1 Nrxn3 Ppp2r5c Ppp2r1a Ppp4r1 Ppp6r3 Cadm1 Tceb2 Ctnnb1 Fxyd1 Eif2b3 Rps25 Hist1h3a Sdc2 Mtch1 Rab1b Ank3 Ppm1a Mcl1 Ppp2r5c Tdg Orc3 Tceb2 Fxyd1 Rps27a Ldb1 Mrpl38 Poll Chchd3 Rps25 Hist1h3a Rab1b Uty Ank3 Lpar6 Wdr33 Orc4 Mtch1 Mrps12 Hmgb1 Mcl1 Tdg Tinf2 Orc3 Chchd3 Nop10 Rps27a Uty Csnk1g3 Lpar6 Erc1 Il6st Mrpl38 Ppp2r5a Wdr33 Poll Mgmt Aen Orc4 Ppp1ca Mrps12 Ube2n Hmgb1 Cacybp Nxf1 Ascc3 Eif3f Nop10 Mrps35 Ewsr1 Erc1 Psenen Ppp2r5a Mgmt Aen Tinf2 Ube2n Pls3 Csnk1g3 Ccnd1 Il6st Cxcl9 Hmgb1 Ascc3 Ppp6r2 Eif3f Ppp1ca Cacybp Nxf1 Xrcc1 Mrps35 Ewsr1 Eml4 Irs2 Psenen Coa5 Hmgb1 Nup85 Thoc2 Eif3e Rps12 Pls3 Ncor1 Ccnd1 Cxcl9 Ccl27a Wdr43 Xrcc1 Ppp6r2 Rras Maf Irs2 Ddx58 Sdc4 Acd Thoc2 Mrpl10 Eml4 Egln1 Aptx Top1mt Nup85 Eif3e Hnf1a Il2 Coa5 Pvrl2 Ctnnd1 Rps12 Ncor1 Smad2 Gabarapl2 Ccl27a Wdr43 Pnkp Rras Maf Ddx58 Sdc4 Lig3 Acd Mrpl10 Hnf1a Egln1 Il2 Pim1 Pop1 Rrp7a Aptx Top1mt Pvrl2 Ctnnd1 Smad2 Gabarapl2 Pnkp Tfpt Mrps5 H2afy Kdm6a Them4 Pim1 Pop1 Rrp7a Lig3 Ppp6r1 M6pr 2210010C04Rik Tspo Xpo1 Rps15 Syvn1 Cldn1 Tfpt Eif2b1 Mrps5 H2afy Kdm6a Them4 Ppp6r1 M6pr 2210010C04Rik Tspo Map2k2 Xpo1 Rps15 Syvn1 Nop10 Nudt18 Gng12 Eif2b1 Rps13 Cldn1 H2afj Atm Ctbp1 Timm13 Fip1l1 Nfrkb Top1 Il1rn Nop10 Xrn1 H2afj Nudt18 Gng12 Map2k2 Rps13 Atm Ctbp1 Timm13 Fip1l1 Nfrkb Top1 Tfg Ripk1 Il1rn Xrn1 Ino80e Ino80d Rap1a Eif3d Nop56 Tfg Ripk1 Rbm28 Ppp1ca Parp1 Ino80e Ino80d Lamtor3 Rap1a Rnps1 Eif3d Nop56 Golph3 Rbm28 Ppp1ca Parp1 Actr5 F11r Lamtor3 Rnps1 Eif4e Etf1 Rps12 Farp2 Rps25 Actr5 Cse1l Golph3 Atp2a2 Eif4e Eif2s3x Etf1 Cdk9 Rpp38 Fcf1 Mrps18c Rps12 H2afv Rdm1 F11r Farp2 Rps25 Cse1l Mrpl14 Gnai3 Eif2s3x Stk11 Ckap5 Mcm10 Atp2a2 Cdk9 Cd47 Rpp38 Fcf1 Mrps18c H2afv Rdm1 Ppp1cb Stk11 Gnai3 M6pr Rexo2 Ckap5 Mcm10 Ndufv3 Eif5b Mrpl14 Men1 Traf3 Cd47 Dag1 Cdh2 Tsfm Rps24 Ppp2r5e Eif5b Ppp1cb M6pr Nmd3 Actr8 Rexo2 Tubd1 Ndufv3 Sumo2 Fbl Men1 Pkn2 Traf3 Ccnd3 Ctnnbip1 Dag1 Cdh2 Tsfm Rps24 Ppp2r5e Sipa1l1 Cxcl12 Nmd3 Actr8 Tubd1 Sumo2 Fbl Ctnnbip1 Ethe1 Pkn2 Gnas Ccnd3 Tipin Ppp6c Gpsm2 Mlxipl Sipa1l1 Cxcl12 Ocln Mrpl37 Parp3 Ethe1 Gas6 Ctla4 Minos1 Ran Ppp6c Gpsm2 Cyp3a11 F2 Gnas Parp3 Tipin Ecsit Mlxipl Gas6 Ocln Ctla4 Minos1 Mrpl37 Cyp3a11 F2 Ube2l3 Tceb2 Sipa1l3 Ran Rps16 Kcnk5 Gnl3 Rps28 Csnk1a1 Ssu72 Ecsit Eif3g Ube2l3 Tceb2 Sipa1l3 Rps16 Smg7 Kcnk5 Gnl3 Rps28 Cdc42 Hpgd Gabarapl1 Csnk1a1 Cldn14 Ssu72 Rif1 Eif3g Hist1h3b Hpgd Gabarapl1 Rps15 Smg7 Vdac3 Cdc42 Gspt1 Cldn14 Heatr1 Mzt2 Rif1 Hist1h3b Cntnap2 Rps15 Arl3 Vdac3 Fxr1 Gspt1 Ghr Heatr1 Per2 Map7d1 Mzt2 Eif3i Fus Irak1 Gnptg Cntnap2 Arl3 Akt2 Fxr1 Ghr Mpg Per2 Map7d1 Arl2 Taok3 Eif3i Fus Epo Bcar1 Irak1 Wnt5b Clcn3 Gnptg Lifr Xpo1 Pop4 Mpg Tubgcp4 Top2b Akt2 Bnip1 Sult1a1 Bcar1 Wnt5b Clcn3 Utp6 Xpo1 Cstf1 H2afz Bloc1s2 Arl2 Taok3 Chd4 Epo Lifr Pop4 Cpsf6 Tubgcp4 Top2b Bnip1 Sult1a1 Dvl1 Utp6 Cstf1 Bloc1s2 Actr1b Cyp2b10 Cpsf6 H2afz Ofd1 Eif4a1 Coa7 Chd4 Hbs1l Actr1b Plg Dvl1 Ofd1 Cep19 Cyp2b10 Lgals1 Ceacam1 Mapk1 Tr nt1 Eif4a1 Coa7 Chchd4 Aspscr1 Pkn1 Daam1 Hbs1l Plg Ube4a Alcam Lgals1 Ceacam1 Tr nt1 Eif4a2 Chchd4 Aspscr1 Pkn1 Daam1 Alcam Rcl1 Clasp1 B9d2 Cep19 Cyp2c44 Mapk1 Eif4a2 Ube4a Dvl3 Rfwd2 Clasp1 Actr1a Cyp2c44 Ndufs2 Dazap1 Bet1 Rcl1 B9d2 Tubgcp2 Uba1 Rps27a Rfwd2 Actr1a Bet1 Dvl3 Fzd8 Ndufs2 Dazap1 Imp4 Rps27a Tubgcp2 Nhp2l1 Mrps36 Mrpl46 Uba1 Hist2h2aa2 Fbf1 Casp3 Phkg1 Fzd8 Imp4 Ssna1 Ppm1b Mrps36 Mrpl46 Mrps18b Phkg1 Nop56 Hist2h2aa2 Fbf1 Ssna1 Casp3 Ppm1b Nhp2l1 Mrps18b Clcn4- H2afx Hist2h2ab Mrps14 Ppp2cb Birc2 Ruvbl1 Clcn4- Nop56 H2afx Hist2h2ab Ino80b Mrps14 Apc Ruvbl1 Xrn2 Ppp2cb Cstf2 Birc2 Clip1 Actr10 Ino80b Csnk2b Mlx Adcy9 Bcl10 Apc Gdf15 Xrn2 Clip1 Actr10 Csnk2b Ppp6c Bcl10 Cstf2 Cbx1 Mlx Il6ra Adcy9 Gdf15 Tr pm7 Peo1 Clp1 Dctn1 Pml Ppp6c Il6ra 2 Rpl5 Cpsf4 Birc3 Tbccd1 Cbx1 Dctn1 Ppp5c Pml Srp14 Tr pm7 Cldn3 Peo1 Clp1 Fbxo4 Rps17 Tln1 2 Rpl5 Cpsf4 Birc3 Tbccd1 Ppp5c Srp14 Ltbr Cldn3 Pmpcb Fbl Fbxo4 H3f3b Atp12a Ndufa2 Rpl5 Rps17 Cldn2 Pop5 Tln1 Ltbr Gpc4 Chchd4 Pmpcb Fbl Ppp2ca H3f3b Pcnt Copa Atp12a Ndufa2 Rpl5 Spcs3 Cldn2 Imp3 Pop5 Ppp2ca Sgta Eif3c Mylk Blnk Gpc4 Chchd4 Cep83 Pcnt Copa Spcs3 Dnaja3 Hist1h2bh Eif3c Sec61g Axin1 Imp3 Rps13 Sgta Cep83 Vps72 Cycs Dnaja3 Mylk Blnk Fbxw7 Hist1h2bh Eif3a Sec61g Magi3 Axin1 Pwp2 Rps13 Ptprd Gfer Det1 Vps72 Mecp2 Cycs Rapgef1 Fbxw7 Eif3a Eif3b Fzd4 Lgals1 Ptprd Nop58 Magi3 Grik3 Pwp2 Dmd Gfer Det1 Coa4 Nhp2l1 Mecp2 Rab3ip Rpl26 Rapgef1 Hspe1 Ninl Eif3b Fzd4 Grik3 Kcnk2 Lgals1 Nop58 Dmd Gabarap Coa4 Nhp2l1 Traf6 Rab3ip Rpl26 Rps4x Tln2 Clic4 Igsf5 Hspe1 Ninl Gosr2 Gabarap Bmpr2 Vangl1 Kcnk2 Kcnn2 Gfm1 Cirh1a Traf6 Mapre1 Ift20 Tubg1 Comt Rps4x Tln2 Igsf5 Bmpr2 Vangl1 Kcnn2 Clic4 Gfm1 Cirh1a Etf1 Mdm2 Mapre1 Tubg1 Comt Egfr Gosr2 Acvr2a Cbx5 Ift20 Mrps36 Etf1 Mdm2 Mapre3 Nde1 Egfr Rps16 Mrps2 Acvr2a Cbx5 Rps14 Vasp Mrps36 Cox7b Mrps2 Pkp2 Fau Tcof1 Ube2j2 Mapre3 Nde1 Rps16 Smad5 Rps14 Vasp Cox7b Pkp2 Gfm2 Fau Tcof1 Ube2j2 Sec22b Fyb Smad5 Myc Gar1 Rapgef4 Gfm2 Pias2 Sec22b Pard6a Fyb Myc Pvrl3 Pias1 Dctn3 Cox20 Gar1 Il11ra1 Prkd3 Rapgef4 Acvr1 Fundc1 Mrpl9 Pias2 Fbxw11 Ift88 Cbx2 Pard6a Pias1 Dctn3 Cox20 Orai1 Il11ra1 Prkd3 Smad1 Acvr1 Pvrl3 Fundc1 Wdr75 Gtpbp4 Nop58 Mrpl9 Fbxw11 Ift88 Cbx2 Sec63 Orai1 Rheb Smad1 Wdr75 Gtpbp4 Nop58 Mapre2 Phc2 Sec63 Prlr Rheb Lrfn3 Ceacam2 Cadm1 Msi2 Pttg1 Mapre2 Phc3 Phc2 Ndel1 Bmp7 Lrfn3 Ube2m Dhtkd1 Prlr Zfyve9 Cd59b Ceacam2 Cadm1 Msi2 Pttg1 Poc1b Phc3 Zw10 Ndel1 Strap Krit1 Bmp7 Mcoln1 Ube2m Nup205 Dhtkd1 Top1 Cdh1 Phb Emd Zfyve9 Cdh1 Krit1 Mcoln1 Cd59b Poc1b Zw10 Nup205 Strap Phb Mtch2 Top1 Emd Mrpl55 Mtch2 Xrn2 Mphosph10 Mrpl55 Eif2s2 Xrn2 Fst Tnpo1 Dazap1 Gspt1 Mphosph10 Rps4x Cbx8 Eif2s2 Fst Ezh1 Tnpo1 Rragc Clic1 Rps4x Dazap1 Gspt1 Herc1 Ash1l Cbx8 Znhit1 Spcs1 Rragc Clic1 Rps17 Nedd4l Mis12 Kat6a Kansl1 Dot1l Ash1l Ezh1 Znhit1 Spcs1 Ifnar2 Ctnnd1 Herc1 H3f3a Timm10b Hist1h2bc Dot1l Cenpm Nedd4l Uba7 Kansl1 Bmi1 Cyp2c29 Nhp2 Rraga Acvr2b Rps17 Mis12 Kat6a Cyp3a13 Ifnar2 Ctnnd1 Utp18 Mrps12 H3f3a Nsf Timm10b Hist1h2bc Hdac11 Cenpm Uba7 Bmi1 Cyp2c29 Nhp2 Il4ra Itgb1 Rraga Acvr2b Sp1 Mrps14 Cyp3a13 Mrpl27 Utp18 Hspe1 Magi1 Mrps12 Eif1ax Nsf Cyp2c44 Pvrl1 Slain2 Hdac11 Il4ra Itgb1 Sp1 Mrps14 Eif5 Hspe1 Mrpl27 Rps3 Magi1 Cyp2c44 Pvrl1 Slain2 Eif5 Eif1ax Snap29 Srp9 Ctnnb1 Clcn7 Kansl2 Atp6v1a Mipep Rps3 Snap23 Nhp2 Mov10 Dsg2 Ppif Ctnnb1 Clcn7 Nhp2 Mrpl11 Fzr1 Nsd1 Kansl2 Akap9 Atp6v1a Mipep Snap23 Snap29 Srp9 Dsg2 Cab39l Tpcn1 F11r Mrpl11 Nsd1 Wdr5 Akap9 Mov10 Dsc2 Ppif Adra1b Cab39l Bmpr1a Ceacam1 Pcdh1 F11r Ubr5 Fzr1 Wdr5 Dsc2 Adra1b Ifnar1 Thpo Ifngr2 Bmpr1a Tpcn1 Kcnq5 Ceacam1 Pcdh1 Kdm1a Eif2s1 Tyk2 Ifngr2 Kcnq5 Csnk2b Mrpl47 Ube2h Ubr5 Kat6b Plk2 Eif2s1 Srp19 Ifnar1 Tyk2 Ifngr1 Thpo ND5 Csnk2b Ube2z Hist1h4h Kdm1a Cep250 Plk2 Srp19 Ifngr1 Prkcz Cd59a Sgta Mrpl47 Ube2h Ube2z Hist1h4h Hist1h4k Kat6b ND5 Ubox5 Cep250 Rps26 Prkcz Cd59a Mrpl46 Stub1 Hist1h4k Sgta Seh1l Rcc1 Ubox5 Rps26 Bdnf Farp2 Rptor Cab39 Mrpl46 Papola Stub1 Stx8 Prkci Seh1l Rcc1 Map2k5 Bdnf Farp2 Prkci Rptor Cab39 Pvrl2 Papola Mbd2 Stx8 Dusp3 Prdm2 Crkl Sco2 Agtr1a Map2k5 Pde3b Pvrl2 Ube3c Mbd2 Kat8 Sirt4 Cyp2c54 Srrm1 Anp32b Dsp Agtr1a Dusp3 Cul5 Prdm2 Kat8 Crkl Atp6v1e1 Srrm1 Eif4g2 Sco2 Pde3b Ube3c Hist1h4d Mbd1 Sirt4 Cyp2c54 Anp32b Mrpl13 Dsp Lamtor3 Mrps17 Cul5 Mbd1 Sirt7 Atp6v1e1 Ndufs8 Eif4g2 Mrpl13 Vamp8 Rps3a1 Mrps17 Hist1h4d Sac3d1 Lamtor3 Sirt7 Sik1 Ndufs8 Vamp8 Ppp1r1b Rps3a1 Hist1h4i Sik1Sac3d1 Ppp1r1b Strada Mrps2 Huwe1 Hist1h4i Top2b Ptk2b Col27a1 Gna12 Gng12 Strada Ptprd Mrps2 Huwe1 Top2b P2rx4 Ptk2b Col27a1 Gna12 Gng12 Cyp2c38 Mrps5 Aurkaip1 Mad2l2 Vdac1 P2rx4 Cdc42 Cyp2c68 Cyp2c38 Ptprd Mtch2 Mrps5 Aurkaip1 Whsc1l1 Kat7 Sirt5 Mad2l2 Sik3 Vdac1 Eif4g1 Sco1 Cdc42 Cul3 Whsc1l1 Kat7 Sirt5 Sik3 Eif4g1 Sco1 Fis1 Hist1h4a Nlk Cyp2c68 F13b Mtch2 Gar1 Cul3 Rala Fis1 Stx18 Spcs2 Cxadr Rps6ka4 Ptprg Hist1h4a Sgk1 Nlk Rac1 F13b Pvr Gar1 Rala Rpl18a Stx18 Spcs2 Cxadr Rps6ka4 Rab14 Rac1 Ptprg Rps29 Sgk1 Pvr Rps5 Rpl18a Atp2a2 Rras2 Fat1 Rps29 Itch Uba6 Xrcc5 Hist1h2be Kansl3 Cep164 Rab14 Tspyl1 Rps5 Zw10 Fat1 Uba6 Immt Atp2a2 Rras2 Pde4d Itch Ppil2 Xrcc5 Hist1h2be Kansl3 Cep164 Rps19 Tspyl1 Ndufa1 Anp32a Immt Zw10 Gna11 Pde4d Epha1 Ppil2 Rps19 Gna11 Crtc2 Epha1 Mrpl54 Ube2g1 Hmgn5 Kdm5b Kdm6b Ndufa1 Anp32a Pam16 Crtc2 Pde4b Mrpl54 Tpgs1 Hmgn5 Kdm5b Kdm6b Galr3 Pam16 Ube2g1 Poli Tpgs1 Galr3 Ppm1a Pde4b Cdhr5 Xrcc6 Brd1 Surf1 Gosr1 Ppm1a Fxyd1 Cdhr5 Xrcc6 Poli EeEedd Brd1 Kdm5a Faf2 Surf1 Parl Gosr1 Dntt Trrap Dnajc19 Parl Rpl14 Kras Hras Fxyd1 Kdm5a Nek7 Faf2 Raf1 Dntt Rap1b Kras Trrap Rab5a Dnajc19 Rpl14 Phka2 Hras Raf1 Nipbl Nek7 Rab5c Rab2a Atp6v1b2 Phka2 Rap1b Rasa1 Hfe2 Ube2r2 Nek1 Rab5a Atp6v1b2 Rap1a Lgals8 Rps21 Brd2 Nipbl Nek1 Rab5c Rab2a Rasa1 Hfe2 Rps3 Ube2r2 Phkb Rap1a Stk4 Lgals8 Rps21 Xrcc4 Brd2 Haus1 Sirt3 Sec11a Cd164 Mtch1 Rps3 Hmgn2 Mrpl14 Stra13 Phkb Stk4 Shc1 Sstr2 Ryk Xrcc4 Haus1 Sirt3 Kdm5c Cmc1 Sec11a Cd164 Mtch1 Mrpl14 Stra13 Hmgn2 Larp1 Grb2 Shc1 Ptprk Nedd4 Wdr48 Rab10 Grb2 Stk3 Sstr2 Ptprk Ryk Wdr48 Setd8 Kdm5c Rab10 Larp1 Sarnp Mtx1 Cmc1 Prkacb Cyp2c37 Cox6c Vdac1 Map4k3 Stk3 Nedd4 Suz12 Arf6 Coa3 Adora1 Setd8 Uqcr11 Sarnp Mtx1 Rpl13a Prkacb Cyp2c37 Cox6c Vdac1 Map4k3 Suz12 Arf6 Coa3 Adora1 Cyr61 Nek4 Uqcr11 Rpl13a Itpr1 Fn1 Itpr1 Atf2 Cyr61 Tceb1 Cdc34 Fancf Nap1l4 Nek4 Fn1 Rps21 Map3k4 Gpr19 Rpl41 Tceb1 Fancf Nap1l4 Rps21 Sec62 Atf2 Cdc34 Rev1 Map3k4 S1pr5 Ndufb10 Cyp7b1 Gpr19 Rpl41 Sec62 Cdc37 Rasgrp2 S1pr2 Rev1 Nek6 Oxa1l Max Cblc S1pr5 Ndufb10 Cdc37 Rasgrp2 Prkaca Daxx Map2k7 Erbb3 Cyp7b1 S1pr2 Mrps35 Wwp2 Chd3 Phf20 Hist1h1e Nek6 Cyp2c70 Hax1 Oxa1l Prkaca Max Map2k7 Cblc Erbb3 Mrps35 Wwp2 Ube2k Atr Chd3 Mbd3 Phf20 Hist1h1e Cyp2c70 Rab5b Hax1 Daxx Ptk2 Ube2k Atr Cyp1a2 Mbd3 Rab5b Ptk2 Nek9 Cyp1a2 Caprin1 Cmc2 Mfn2 Mrpl28 Hspb1 Lgr5 Jmjd6 Caprin1 Cmc2 Mfn2 Mrpl28 Nf1 Hspb1 Cyp2c54 Lgr5 Sirt2 Jmjd6 Nek9 Cdc37 Mtx2 Mrps21 Nf1 Sirt2 Cyp2c54 Mrps21 Map2k1 Stmn1 Rps6kb2 Cdc37 Stau1 Nin Stmn1 Rps6kb2 Rab17 Them4 Stau1 Nin Map2k1 Cyp2c70 Cyp2c29 Tr ip12 Rab17 Them4 Mllt4 Sucnr1 Tr ip12 Atrip Rpl6 Cyp2c70 Cyp2c29 Mllt4 Nrg4 Sucnr1 Atrip Phf20l1 Rabl3 Itga5 Rpl6 Ube3b Nrg4 Ube2l3 Phf20l1 Hdac10 Kdm4a Kdm3b Rabl3 Itga5 Cse1l Vdac3 Ube3b Brd3 Mfn1 Ube2l3 Pmf1 Hdac10 Kdm3b Arf4 Usp30 Kdm4a Cse1l Vdac3 Ppm1b Rps6kb1 Immt Brd3 Mfn1 Ppm1b Chuk Immt Wwp1 Tdrd7 Pmf1 Hmgn1 Arf4 Gnb2 Usp30 Chuk Rps6kb1 Cyp2b10 Tdrd7 Rab32 Dnm1l Gnb2 Rps26 Wwp1 Pcgf3 H1f0 Hmgn1 Cyp2b10 Rab32 Dnm1l Rpl12 Gsk3b Ramp2 Map1lc3a Rps26 Pcgf3 H1f0 Insr G3bp1 Rpl12 Rpl10a Gsk3b Ramp2 Map1lc3a Uba3 Insr G3bp1 Lonp1 Rpl10a Wdr5 Ppp3ca Uba3 Eme2 Asxl2 Jade1 Dlg1 Lonp1 Wdr5 Actr1b Eme2 Haus2 Asxl2 Jade1 Golga1 Actr1b Ppp3ca Asxl1 Hdac5 Dlg1 Rpl24 Cox18 Haus2 Mcrs1 Asxl1 Jmjd1c Golga1 Cyp2c40 Vtn Gfer Ube3a Hist1h1c Hdac5 Rpl24 Rras Cox18 Ube3a Mcrs1 Hist1h1c Jmjd1c Csnk1d Cyp2c40 Rab18 Vtn Gfer Pak2 Rps14 Ncoa1 Gng5 Timm9 Map2k4 Trim37 Setdb2 Csnk1d Rab18 Ndufa5 Rras Stat5b Cyp2c40 Pak2 Rps14 Ncoa1 Gng5 Timm9 Ube2f Pgam5 Map2k4 Trim37 Setdb2 Ndufa5 Stat5b Cyp2c40 Atp5f1 Galr3 Mgrn1 Ing5 Ube2f Birc6 Pgam5 Atp5f1 Ppp5c Araf Galr3 Atad3a Mgrn1 Ppp1r2 Ing5 Usp14 Birc6 Mau2 Ndufa10 Orai3 Ppp5c Araf Atad3a Keap1 Ppp1r2 Haus4 Sdccag8 Spc24 Mau2 Chtf8 Ndufa10 Ptcd3 Usp14 Nck1 Sdccag8 Kdm7a Pmpcb Orai3 Mrpl10 Keap1 Spc24 Chtf8 Hmgn5 Nck1 Mrpl10 Rchy1 Anapc1Anapc133 Haus4 Kdm7a Hsd11b1 Pmpcb Ptcd3 Sec61a1 Hmgn5 Nfkb1 Rchy1 Hsd11b1 Gnb1 Eif2a Timm8b Pik3r2 Sec61a1 Nfkb1 Pik3r2 Atg14 Smyd2 Pde4dip Gnb1 Eif2a Timm8b Traf2 Atg14 Ube2e2 Smyd2 Esco1 Ing4 Pde4dip Traf2 Ube2e2 Cep44 Esco1 Ing4 Hist1h1d Stim2 Sfi1 Cyp2c55 Cyp2c50 Gps1 Cep44 Meaf6 Bcs1l Hist1h1d Stim2 Ube2j1 Sfi1 Spc25 Cyp2c55 Cyp2c50 Ndufb11 Gps1 Rab3ip Rps18 Meaf6 Ndufs4 Bcs1l Ube2l6 Set Gfm1 Chchd3 Rpl11 Rps18 Ube2j1 Spc25 Ndufb11 Ndufs4 Tsfm Rab3ip Ube2l6 Set Rpl18 Hmgb3 Larp4 Gfm1 Chchd3 Rpl11 Smyd3 Ifi47 Tsfm P2ry2 Rpl18 Hist1h1b Egfr Pik3r1 Psmc2 Smyd3 Ing3 Hmgb3 Ifi47 Larp4 Egfr Pik3r1 P2ry2 Zfyve1 Psmc2 Ing3 Nap1l1 Gfm2 Usp10 Hist1h1b Zfyve1 Syvn1 Msl3 Nap1l1 Usp9x Gpr146Gpr146 Syvn1 Msl3 Gfm2 Mrpl15 Usp9x Usp10 Lgr4 Rpl10 Haus7 Pds5a Mrpl15 Lgr4 Ube2e1 Haus7 Pds5a Minos1 Opa1 Rpl10 Cops3 Cdkn1a Mrpl34 Minos1 Rpl28 Ube2e1 Fancl Pcgf5 Opa1 Ecsit Ndufs6 Cops3 Itga5 Cdkn1a Mrpl34 Socs1 Rpl28 Fancl Pcgf5 Phb2 Ecsit Uba1 Ndufs6 Rps23 Itga5 Braf Socs1 Phb2 Cx3cr1 Uba1 Rps23 Lama3 Braf Ube2n Ctnna1 Cx3cr1 Ube2d3 Herc2 Ncoa3 Cox17 Sirt5 Lama3 Ube2n Ctnna1 Rhot1 Ube2d3 Herc2 Ncoa3 Ncoa2 Cox17 Sirt5 Tgfa Haus8 Prmt3 Hist1h1e Ube2w Lhpp Rhot1 Tgfa Wipi2 Ube2d2a Haus8 Prmt3 Ncoa2 Morf4l2 Hist1h1e Wipi2 Mipep Ube2w Uba2 Morf4l2 Lhpp Lphn2 Cox19 Mipep Uba2 Ube2d2a Npm3 Timm8a1 Ufc1 Dusp16 Lphn2 Cox19 Npm3 Timm8a1 Cops2 Ufc1 Dcaf8 Mapk9 Dusp16 Mtor Cyp2c50 Fbxw8 Dcaf8 Mapk9 Mtor Psmd6 Rbbp4 Atp6v1h Cops2 Cyp2c50 Fbxw8 Pcgf6 Carm1 Psmd6 Rbbp4 Atp6v1h Ube4b Pcgf6 Carm1 Map2k2 Wipi1 Atg16l1 Nbr1 Ube4b Map2k2 Gprc5c Wipi1 Atg16l1 Nbr1 Sae1 Tomm20 Pmpca Ep400 Tomm20 Mras Gprc5c Sae1 Psmd5 Npm1 Anp32e Abl2 Ube2q1 Pmpca Mapk14 Ep400 Gnb2l1 Ndufs1 Mras Psmd5 Npm1 Anp32e Arf5 Mapk14 Abl2 Naa25 Ube2q1 Gnb2l1 Ndufs1 Naa25 Ube2q2 Ncoa6 Oaz1 Arf5 Mrpl12 March5 Atg16l2 Ye ats4 Naa20 Rpl10a Ube2e3 Ube2q2 Cep290 Ncoa6 Oaz1 Mrpl12 March5 Atg16l2 Rpl13 Naa20 Rpl10a Ube2e3 Cep290 Ye ats4 Mtfp1 Akap9 Prmt6 Rpl13 Jup Mtfp1 Tr im28 Akap9 Prmt6 Grpel1 Dusp1 Psme2 Brd8 Jup Grpel1 Tr im28 Jak1 Vhl Psme2 Brd8 Jak1 Dusp1 Rpl26 Vhl Ube2a Rcbtb1 Ctnna2 Ube2a Psmd7 Ctnna2 Ndufb6 Tomm70a Rpl26 Klhl9 Asf1a Rcbtb1 Lace1 Mtif2 Tefm Anapc11 Psmd7 Ndufb6 Tomm70a Zbtb20 Anapc11 Ube4a Klhl9 Fopnl Epc1 Asf1a Lace1 Mtif2 Tefm Mrpl1 Zbtb20 Srp68 Tnfrsf1a Dusp6 Ube4a Fopnl Rybp Epc1 Rab35 Ndufa11 Mrpl1 Srp68 Dusp6 Fau Rybp Rab35 Tnfrsf1a Sos1 Fau Psme3 Ndufa11 Ptcd2 Nedd8 Sos1 Ya f2 Map2k3 Psme3 Ya f2 Tr mt10c Ptcd2 Nedd8 Vtn Map2k3 Pml Tr mt10c Vtn Pml Rcbtb2 Ndufab1 Tomm22 Gcgr Dmap1 Ndufb3 Gcgr Rpl28 Morf4l1 Rcbtb2 Gadd45a Ndufb3 Ndufab1 Tomm22 Rhobtb1 Herc4 Dmap1 Cox6a1 Rpl28 Socs3 Hook2 Nasp Morf4l1 Tarbp2 Gadd45a Timm10 Rps27l Rhobtb1 Herc4 Arl1 Cox6a1 Plce1 Socs3 Hook2 Nasp Tarbp2 Timm10 Timm44 Rps27l Plce1 Bcl2l1 Mapkapk2 Prmt7 Arl1 Supv3l1 Timm44 Numa1 Abl1 Bcl2l1 Mapkapk2 Uqcc2 Ddi2 Psmc1 Prmt7 Ndufaf6 Supv3l1 Numa1 Abl1 Ikbkb Cyp3a11 Uqcc2 Ndufaf6 Ikbkb Cyp3a11 Ddi2 Psmc4 Psmc1 Ash2l Ndufa7 Psmc4 Ash2l Ufm1 Rbbp5 Ndufa7 COX3 Ufm1 Cyp3a41a Rps2 Rnf7 AW558785 Rbbp5 COX3 Akt1 Usp5 Zak Phb Rnf7 Eri3 Rab1b Rpl34 AW558785 Nedd1 Ndufv1 Cyp3a41a Rps2 Hook3 Akt1 Eri3 Cyp2e1 Tomm6 Usp5 Sirt3 Zak Phb Rab1b Rpl34 Nedd1 Ndufv1 Rpl6 Psmd10 Hook3 Gadd45g Mapk3 Hsd3b5 Cyp2e1 Tomm6 Nubpl Sirt3 Rpl6 Psmd10 Gadd45g Mapk3 Hsd3b5 Nubpl Rps27 Smc4 Lrpprc Rpl23 Ikbkg Rpl7 Rpl36 Akt2 Nras Smc4 Rab43 Rhebl1 Lrpprc Rps27 Rpl23 Ikbkg Rpl7 Rpl36 Map3k13 Il1r1 Akt2 Nras Map3k13 Kiz Rab43 Rhebl1 Timm23 Timm21 Srp72 Set Il1r1 Stx4a Psmd11 Kiz Pibf1 Dpy30 Tfg Timm23 Timm21 Mrps16 Rpl4 Srp72 Set Stx4a Psmd11 Pibf1 Tfg Mrps16 Mapk1 Gpr39 Dpy30 Rpl4 Psma1 Ndufaf2 Mapk1 Gpr39 Fbxl4 Psma1 Ndufaf2 Haus4 Mknk1 Fbxl4 Ncaph2 Rab21 Haus4 Mknk1 Pcm1 Ncaph2 Rab21 Uba5 Tgfbr1 Pcm1 Actr6 Cyp2d26 Sdhaf2 Uba5 Map3k5 Mrpl27 Actr6 Dcaf11 Abhd12 Tgfbr1 Cep63 Cyp2d26 Sdhaf2 Mknk2 Map3k5 Taok1 Mrpl27 Dcaf11 Abhd12 H1f0 Mknk2 Taok1 Psmd9 Cep63 Letm1 Mrpl13 Rps19 Psmg1 Psmd9 Psme1 Timm17b Letm1 H1f0 Rps6ka1 Rps19 Psmg1 Timm17b Mrpl13 Bnip1 Ykt6 Cspp1 Taco1 Usp48 Olfr56 Psme1 Cep89 Trim14 Rps6ka1 Bnip1 Cspp1 Taco1 Usp48 Ndufs5 Metap2 Crk Surf1 Ykt6 Atp6v0d1 Ndufs7 Sirt2 Olfr56 Cep89 Ktn1 Ndufs5 Trim14 Usp4 Metap2 Rbbp4 Crk Surf1 Cep57 Ddhd2 Atp6v0d1 Ndufs7 Sirt2 Mrpl12 Psmd3 Plk3 Atp5d Ktn1 Usp4 Rbbp4 Rpl12 Mrpl12 Psmd3 Cep57 Plk3 Cep350 Ddhd2 Arl8b Atp5d Rpl12 Stx17 Cep350 Arl8b Timm50 Ndufaf3 Hspa5 Pet100 Stx17 Ankhd1 Timm50 Ndufaf3 Samm50 Hspa5 Taok3 Pet100 Ankhd1 Iqcb1 Brcc3 Tr im23 Taok3 Iqcb1 Samm50 Acad9 Brcc3 Usp15 Ndufaf4 Tr im23 Hist1h1c Acad9 Usp15 Ndufaf4 Hist1h1c Cyp3a25 ND6 Cox20 Rpl14 Atp5e Ndufaf1 Pepd Cyp3a25 ND6 Rpl14 Psme4 Psma5 Ndufaf1 Pepd Cox20 Tacc1 Atp5e Metap1 Rela Rpl18a Psme4 Psma5 Atpaf2 Mrpl16 Tacc1 Metap1 Fas Rela Mrps21 Rpl18a Cep85l Atpaf2 Mrpl16 Rnf114 Rab5a Psma2 Cep85l Otub1 Rnf114 Rab5a Fas Cyp3a13 Ktn1 Mrps21 Mta3 Cyp3a13 Ktn1 Bet1 Psma2 Mta3 Ndufa8 Ptrh2 Diablo Tomm7 Ndufaf7 Usmg5 Otub1 Srpr Mta2 Ptrh2 Diablo Tomm7 Ndufaf7 Bre Srpr Cenpj Gpr125 Bet1 Ndufa8 Usmg5 Map3k2 Mta2 Gpr125 Cep85 Ankrd17 Mrps7 Bre Uchl5 Cenpj Map3k2 Cep85 Ankrd17 Mrps7 Cops4 Uchl5 Cops7a Abcf3 Tomm5 Cops4 Cops7a Ruvbl2 Bad Dhtkd1 Abcf3 Rpl17 Ruvbl2 Rsl24d1 Tacc2 Tomm5 Bad Dhtkd1 Dek Mrpl24 Rpl17 Map3k7 Mterf3 Rsl24d1 Tacc2 Dek Mta1 Mrpl24 Rpl37a Mterf3 Psmd1 Map3k7 Map3k11 Mta1 Rpl37a Map3k11 Psmd1 Tpp2 Cops6 Cops5 Rpl7a Cops5 Nap1l4 ND4L Psmb2 Tmem126a Tpp2 Cops6 Sult1a1 Fus Rpl7a Mrpl4 Nap1l4 ND4L Psmb2 Tmem126a Rps11 Bet1l Fus Cyp2d9 Fgf1 Psmd13 Sult1a1 Rps11 Mrpl4 Mterf4 Bet1l Cyp2d9 Afg3l1 Fgf1 Psmd13 Atp5l Afg3l1 Mterf4 Vti1b Tmx3 Tab2 Atp5l Afg3l2 Nap1l1 Stx16 Vti1b Psmd12 Baz1a Tmx3 Afg3l2 Nap1l1 Tab2 Stx16 Psmd12 Psmb1 Brd7 Baz1a Ubn1Bptf Golph3 Mrrf Lonp1 Psmb1 Brd7 Ubn1Bptf Golph3 Mrrf Spg7Spg7 BrapBrap Lonp1 Rpl39 Dpp7 Hmgn1 Pdgfa Mrpl28 Psmg2 Cntrl Rpl39 Psmd9 Dpp7 Hmgn1 Psmg2 Myo1b Cntrl Rpl27 Psmd9 Mta2 Pdgfa Sco2 Mrpl28 Brd9 Myo1b Rpl27 Mta2 Sco2 Brd9 Aspscr1 Ewsr1 Cluh Psmd1 Rala Baz1Baz1bb Ubn2 Aspscr1 Ewsr1 Cluh Psmd1 Pds5b Lats1 Rala Timm22 Ubn2 Pds5b Timm22 Rpl7 Vti1a Myo1e Dpy30 Phb2 Rbbp7 Lats1 Rpl7 Vti1a Nsf Psmf1 Myo1e Rbbp7 Dpy30 Phb2 Rbbp7 Arf6 Nsf Psmf1 Rbbp7 Dlg3 Zap70 Arf6 Psmc5 Chrac1 Dlg3 Zap70 Stx5a Psmc5 Chrac1 Stx5a Mybbp1a Scrib Hpgd Nae1 Ndufa4 Psmd12 Ppargc1a Psma3 Mpp5 Mybbp1a Cul4b Scrib Hpgd Nae1 Ndufa4 Psmd12 Sco1 Ppargc1a Psma3 Mpp5 Cul4Cul4b a Mrps11 Myo1d Bbc3 Cyp2e1 Sco1 Cul4a Mrps11 Myo1d Bbc3 Cyp2e1 Rps5 Ya p1 Igf1 Rps5 Myo1c Rpl18 Rsf1 Ya p1 Igf1 Smarcal1 Ptpn11 Mrpl15 Rpl18 Rsf1 Myo1c Wwtr1 Ptpn11 Cyp1a2 Mrpl15 Smarcal1 Cyp2d22 Dlg1 Wwtr1 Cyp1a2 Chd9 Mrps18b Cyp2d22 Clpx Chd7 Chd9 Mrps18b Hsd17b6 Clpx Dlg1 Chd8 Ercc1 Chd4 Insr Stx18 Sec22b Chd7 Chd8 Rad23a Ercc1 Chd4 Hsd17b6 Atp5j2 PsmcPsmc44 Ddi2 Insr Stx18 Sec22b Chd6 Rad23a Atp5j2 Ddi2 Llgl2 Spp1Spp1 Psmb3 Chd6 Psmd8Psmd8 NpeppsNpepps Llgl2 Ercc4 Npm1 Psmd8 Ercc4 Npm1 Ctnna1 Vamp5 Eef1g Abcf1 Rhoa Psmd8 Rpl35a Ctnna1 Wwc1 Vamp5 Rad51d Eef1g Abcf1 Rhoa Tufm Rpl8 Rpl35a Inadl Wwc1 Nbn Uqcrq Rad51d Mus81 Tufm Rpl8 Inadl Rpl13a Nbn Uqcrc1 Uqcrq Mus81 Rpl13a Xpc Rad23b Uqcrc1 Rpl38 Psmc2 Pink1 Use1 Psmc2 Mybbp1a Xpc Rad23b Atp5j Rps6 Gnb1 Pink1 Use1 Shfm1 Dnaja3 Atp5j Rps6 Rpl38 Mybbp1a Limd1 Rpl37a Shfm1 Dnaja3 Limd1 Vegfa Gnb1 Rpl37a Psma4 Rad50 Psma6 Ict1 Sav1 Vegfa Stx6 Psma6 Psma4 Rad50 Ict1 Sav1 Stx6 Psmc3 Top3b Nf2 Psmc3 Top3b Rpl9 Rpl37 Nf2 Rpl24 Psmd4 AcsfAcsf33 Rpl9 Rpl37 Cct7 Psme2Psme2 PsmdPsmd77 Rassf6 Rpl24 Psmd4 Rassf6 Psmd5 Mob1b Rps23 Psmd5 Mob1b Rps23 Ercc5 Calm1 Psma7 Ercc5 Cetn2 Hsd17b2 Psmd2 PsmdPsmd66 Calm1 Mrpl1 Psma7 PoPolele44 Rbx1 Cetn2 Hsd17b2 Ndufa6 PdiaPdia55 Psmd2 Mrpl1 Ndufa6 Rpl3 Gosr2 Rgl2 Rpl3 Ralbp1 Gosr2 Rgl2 Ralbp1 Psmc6 Ndufa9 Cebpb Snap29 Psmc6 Ndufa9 Mrpl3 Cebpb Rpl34 Rpl17 Snap29 Cyc1 Mrpl3 Cxcl10 Rpl34 Rpl17 Psmd2 Cyc1 Aadac Snap23 Psme1 Erap1 Cxcl10 Gng5 Psmd2 Aadac Myo1b Gng5 Rab5c Snap23 Xpa Psme1 Erap1 Myo1b Xpa Eef2 Rab5c Eef2 Rpl23a Psmb9 Sec6Sec633 Ssbp1 Dek Sirt1 Bnip3l Stx8Stx8 Psmb9 Ssbp1 Ddb1Ddb1 SsSsbb Bag3 Psmc1 Dek Sirt1 Bnip3l Rpl36 Vamp8 Psmb10 Spcs3 Lrp1 Ndufc2 Ndufv2 Bag3 Psmc1 Comt Rpl36 Vamp8 Psmb10 Spcs3 Lrp1 Cyp2d10 Ndufc2 Ndufv2 Comt Mrps22 Mcm6 Cyp2d10 Mrpl22 Psmb5 Mrps22 Dnm1l Psmb5 Rpa2 Mcm6 Mrpl22 Psmd11 Dnm1l Calm2 Rpa2 Ndufb7Ndufb7 Psmd11 Apeh Calm2 NrNripip11 Rfc1 Pold2 Apoe Rpl36aRpl36a Apeh Mrps16 Rfc1 Lig1Pold2 Apoe Mrps16 F11 Psmb7 Pole3 Lig1 Rpl31 Psma2 Mllt4 F11 Psmb7 Rfc3 Pole3 Psma2 Psma1 Tnfrsf1b Cxcl1 Mllt4 Rfc3 Hnf4a Psma1 Cul4a Tnfrsf1b Cxcl1 Psmb4 Hnf4a Psmd3 Rhot1 Vamp4 Psmb4 Srd5a1 Rpl22l1 Psmd3 Cul4a Calm3 Rhot1 Vamp4 Psmb8 Rpa3 Srd5a1 Rpl22l1 Calm3 Psmb8 Rpa3 Ndufa13 Rpl30 BlmhBlmh Pla1a Cyp17a1 Rfc5 Polr2h Ndufa13 Rpl30 Mmp14 Pla1a Cyp17a1 Rfc5 Polr2h Ndufs3 Mmp14 Stx2 Ndufs3 Psmc5 Bag4 Stx2 Gosr1 Psmc5 Rad23b Exoc2 Gosr1 Pepd Psmb6 Bag4 Rad23b Exoc2 Met Pepd Psmb6 Spcs1 Cox7c Met Timm8a1 Stx7 Spcs1 Rnaseh2a Hnrnpul1 Cox7c Psmb1 Timm8b Timm8a1 Stx7 Rnaseh2a Hnrnpul1 Ndufb4 St13 Psmb1 Lrpprc Rnaseh2b Pgam5 Lrpprc Timm8b Rnaseh2b Rplp0 St13 Mlkl Pgam5 Tbk1 Rplp0 Mlkl Dnpep Tbk1 Spcs2 Rasal2 Rpa1 Ifitm3 Dmgdh Dnpep Stradb Spcs2 Vegfb Rasal2 Masp1 Rpa1 Kpna1 Ifitm3 Cct8 Npr2 Mrpl35 Dmgdh Stradb Metap1 Masp1 Kpna1 Atp5o Vegfb Abhd10 Psmd14 Cct8 Npr2 Mrpl35 Metap1 Atp5o Psmd14 Mlycd Metap2Metap2 Abhd10 Rfc2 Mlycd Kmo Mrpl18 Mrpl18 Prkce Fgfr4 Rfc2 Kmo Abhd11 Pm20d1 Prkce Ets2 Fgfr4 Abhd11 Pm20d1 Ets2 Prss36 Psmb2 Ddb1 Cyp2d26 Prss36 Ndufb8 PsmaPsma66 Psmb2 Ddb1 Cyp2d26 Atg2a Rfc4 Ndufb8 Rpl21 Mrpl2 Rpl4 C1ra Mrpl2 Atg2a Rfc4 Rpl21 Ralb Fgfr2 Uqcc1 Rps27l Rpl4 C1ra Scrn2 Ralb Klk1b4 Fgfr2 Aip Uqcc1 Pmpca Rps27l Ift57 Psmb3 Scrn2 Scrn3 Ift57 Rpl22 Klk1b4 Slc44a1 H2- Aip Pmpca Srp9 Rpl22 Psmb3 Scrn3 Slc44a1 H2- Sec11c Srp9 Psen1 Mcm7 Bcl2l13 Park7 Gamt Uba52 Metap1d Sec11c Gamt Psma3 Rnpep Gng11 Rps27 Mrpl18 Psen1 Mcm7 Bcl2l13 Park7 Uba52 Metap1d Tfam Psma3 Rnpep Gng11 Rps27 Mrpl18 Rab14 Cd1d2 Taco1 C1qbp Tfam Bsg Rpl32 Rab14 Cd1d2 Taco1 C1qbp Rpl32 Hmgcr Pomp Bsg Ndufa12 Rps9 Hmgcr Fis1 Rpl23 Ndufa12 Rps9 Ke6 Fis1 Cmc1 Rpl23 Psmg4 Pomp Ke6 Cmc1 Psmg4 Immp2l Psmd13 MtifMtif33 Immp2l SrSrprprbb Rnaseh2cRnaseh2c Psmd13 Ssbp1 Cmc2 Uqcrfs1 Mrps23 Abhd14b Ssbp1 Cmc2 Oxa1l Uqcrfs1 Eif5a Mrps23 Hsp90ab1 Abhd14b Xpnpep3 Cox4i1 Xpnpep3 Coa3 Scpep1 Oxa1l Cox4i1 Eif5a Rps10 Hsp90ab1 Hsd3b2 Coa3 Scpep1 Abcg2 Rps10 Hsd3b2 Sec11a Abcg2 Uqcr10 Psmc6 Proc Mrpl32 Parl Sec11a Uqcr10 Cox7a2l Psmc6 Proc Mrpl32 Parl Cox7a2l Prss8 Htra2 Cd1d1 TrTriap1iap1 Apeh Prss8 Htra2 Clpp Cd1d1 Apeh Mrps24 Mrps24 Rab2a Efna1 2010111I01Rik Psma7 Rab2a Efna1 2010111I01Rik Psma7 Psma4 Scpep1Scpep1 Adipor1 Rpl27 Abhd12 Dpp7 Tgm2 Psma4 Nrd1 Srd5a3 Habp2 Adipor1 Rpl27 Abhd12 Dpp7 Tgm2 Mrpl20 Hsp90aa1 Nrd1 Srd5a3 Atg12 Habp2 Psmc3 Dpp3 Hsd3b6 Timm10 Atg12 Mrpl20 Chordc1 Hsp90aa1 Psmc3 Dpp3 Timm10 Rpl7a Amz2 Ccs Chordc1 Hsd3b6 Tomm70a Opa1 Rpl7a Amz2 Sec61a1 Fen1 Ccs Tomm70a Sec61a1 Opa1 Rpl15 Psen2 Fen1 Eef1d Psma5Psma5 Yme1l1 Hsd3b5 Rpl15 Bace1 Yme1l1 Hsd3b5 Bace1 Sppl3 Pcna Mrpl23 Eef2k Rnpepl1 Sppl3 Pgpep1 Pcna Vac14 Mrpl23 Eef2k Rnpepl1 Vac14 Mrps6 Grpel2 Pgpep1 Capn7 Mrps6 Trap1 Psmb4 Grpel2 Dnajc19 Cflar Psmb9 Capn7 Psmb4 Pold3 Trap1 Dnajc19 Cflar Capn10 Rplp1 Psmb9 Ube2i Npepps Capn10 Pold3 Rplp1 Cyp2d22 Npepps Psmd4 Cyp2d22 Ube2i Rpl38 Rpl19 Psmd4 Atg5 Rpl38 Sec61g Polr3a Rpl19 Sec61g Polr3a Atg5 Ranbp1 Tomm40 Clu Cct5 AdiporAdipor22 Mtx2 Grpel1 Ranbp1 Tomm40 Clu Cct5 Hp Hsd11b1 Mtx2 Grpel1 F12 Hp Hsd11b1 Mtx1 Sec62 Rpl27a Sec61a2 Sec62 Mtx1 Erap1 Srp72 Rpl27a Psmd14 Rab10 Erap1 Mmp19 Sec61a2 Srp72 Ptma Psmd14 Rab10 Upf3b Mfn2 Rnpep Mmp19 Ptma Ece1 Mfn2 Rps7 C1s2 Rnpep Psmb5 Upf3b Ece1 Rps7 C1s2 Psmb5 Lonp2 Upf3Upf3aa Mfn1 Rps27rt Pm20d1Pm20d1 Clpp Sept9 Lonp2 Mfn1 Rps27rt Blmh Clpp Sept9 Aaas Aaas Blmh Sept1 Psmb7 Sept1 Rps8 Ctso Cox7a2 Psmb7 Timm9 Ttc19 Rps8 Ctso Hpn Cox7a2 Hpn Thoc1 Timm9 Ttc19 C1s1 Immp1l Capns1 Rpl37 Scrn3 Immp1l Thoc1 Rpl37 C1s1 Scrn3 Eef1a1 Capns1 Eif4ebp2 Tmprss6 Srp14 Sept2 Eef1a1 Eif4ebp2 ND2 Mtfp1 Tmprss6 Srp14 Sept2 Cth ND2 Mtfp1 Cth Pam16 Rab11b Ndc1 Cela1 Lactb Pam16 Sdhaf2 Mrpl21 Psmb6 Prep Rab11b Ndc1 Cela1 Uqcrb Lactb Cyp2d34 Rangap1 Sdhaf2 Uqcrb Mrpl21 Psmb6 Prep Cyp2d34 Rangap1 Hsd17b6 Ncbp2 Mmp15 Hsd17b6 Ncbp2 Mmp15 Sdsl Mrpl19 Stip1 Polg Atp5c1 Sdsl Mrpl19 Dnajc11 Xpnpep1 Stip1 Polg Mrpl4 v Atp5c1 Dnajc11 Xpot Xpnpep1 Scrn2 Igtp Xpot Mrpl4 Scrn2 Nos3 Nos3 Sppl2a Psmb8 Sppl2a Cyp2d9 Bcs1l Sec61bSec61b MrMrps25ps25 Psmb8 Cyp2d9 Bcs1l Npepl1 Kpnb1 Mtif2 Npepl1 Rplp2 Kpnb1 Hgfac Nup210l Mtif2 Rpl9 Rplp2 Nup210l Rpl9 Rpl35a Hgfac Fkbp11 Igsf8 Rpl35a Rpl39 Fkbp11 Igsf8 Cyp2d11 Rpl39 Snd1Snd1 Rps20 Ifitm3 Cyp2d11 Usmg5 Rps11 Rps20 Clpb Rps11 Dnpep Cox15 Clpb Ifitm3 Yme1l1 Ccbl1 Dnpep Yme1l1 Cox15 Ccbl1 Casp9 Senp2 Casp9 Thoc5 Senp2 Thoc5 Timm44 Rpl8 Mrps31 Timm44 Rpl8 Mrps9 Mrps31 Cct3 Cct4 Aox3 Mrps9 Rpsa Tfb2m Rpl36al Aox3 Rpsa Cct3 Cct4 Gemin2 Dap3 Gemin2 Tfb2m Rpl36al Ece1 Dap3 Tgs1 Mtpap Ece1 ND3 Mtpap Mrpl17 Cyp2d12 Tgs1 ND3 Mrpl17 Cyp2d12 Dmd Mrps27 Eif1b Eif2b2 Dmd Mrps27 Eif1 Eif1b Eif2b2 Slc25a28 Upf2 Eif1 Alyref Pnn Slc25a28 Mrpl30 Ccbl2 Mrps26 Upf2 Alyref Pnn Polrmt Mrps11 Rpl36a Mrpl30 Ccbl2 Mrps26 Mrps10 Polrmt Mrps11 Rpl36a Ece2 Mrps10 Mrps30 Ece2 Ndufb9 EarsEars22 Mrps28 Mrps30 Alyref2 Slc25a37 Sds Eif3m Mrps15 Ndufb9 Mrps28 Alyref2 Slc25a37 Pkp2 Sds Eif3m Mrpl43 Mrps15 LonpLonp22 Pkp2 Mrpl43 Supv3l1 Tmem126a Glrx5 Supv3l1 Uqcrc2 Thoc3 Tmem126a Mrps22 Dpp8 Uqcrc2 Glrx5 Thoc3 Ptcd3 Mrps23 Mrps22 Dpp8 Lars Ptcd3 Mrps23 Sppl2b Dsg2 Lars Mrpl40 Sppl2b Dsg2 Lars2 Ppia Mrpl40 Lars2 Mrps34 Ppia Tomm20 Hspa5 Aldh4a1 Qars Mrps34 Tomm20 Hspa5 Aldh4a1 Qars Mrpl41 Mrpl41 Mrpl44 Rbm8Rbm8aa Sec13 Mrps7 Aadac Mrpl44 Nup88 Sec13 ATP8 Aadac Ifitm2 Nup88 ATP8 Ptcd2 Cmpk1 Cars Gars Mrps33 Tpr Cars Mrps33 Ifitm2 Tpr Nup50 Ptcd2 Mrpl16 Nrd1 Cmpk1 Gars Nup50 Xpo5 Mrpl16 Nrd1 Dpp3 Xpo5 Rplp0 Dpp3 Cda Rplp0 Abhd4 Dsp Cda Cct2 Abhd4 Dsp Rps15Rps15aa Cct2 GlrxGlrx Mrpl53 Mrpl51 Mrpl53 Paip1 NdufNdufafaf22 Aox1 YaYarsrs22 Mrpl51 Bsg Nup85 Paip1 Gmcl1 Prep Aox1 Mrpl45 Rpl3 Dpp9 Mrpl45 Bsg Nup85 Eif2b4 Gmcl1 Prep Ranbp2 Rpl3 Dpp9 Nup43 Ranbp2 Eif2b4 Nup43 Umps Pdia3 Nup62 Nup37 Umps Hars Pdia3 Prnp Nup62 Ddc Prnp Hsd17b2 Nup37 Fbxl20 Ddc Yars Hars Canx Hsd17b2 Fbxl20 PoPolr2clr2c Tars Yars Canx Timm21 Asb3 Usp25 Tars Hspa8 Magoh Timm21 Asb3 Usp25 Hars2 Hspa8 Magoh Mrps24 Hars2 Cyp2d40 Xiap Wars Calr Mrps24 Cyp2d40 Ncbp1 Xiap Wars Calr Rhbg Cyp2d10 Eif3h Timm23 2010107E04Rik Fkbp8 Rhbg Cyp2d10 Eif4b Ncbp1 Eif3h Timm23 2010107E04Rik Socs7 Tmed7 Fkbp8 Eif4b Eif2b5 Thoc2 Rpl31 Socs6 Socs7 Abhd11 Cxadr Tmed7 Eif2b5 Thoc2 Rpl31 Nacc2 Socs6 Abhd11 Polr2b Cxadr Apoe Nacc2 Eif3l Hpn Polr2b Ddx21 Apoe Eif3l Nars2 Usp19 Hpn Ddx21 Rb1cc1 Nars2 Cd9 Rb1cc1 Usp19 Bmp1 Cd9 Asb6 Fbxl3 Usp33 Bmp1 Eif3k Eif2s3y NdufNdufafaf33 Mrpl24 Asb6 Fbxl3 Usp33 Eif3k Eif2s3y Mrpl24 Ssr4 Nup54 Rpl23a Iars2 Hspa13 Ssr4 Nup54 Rpl23a Smurf2 Usp18 Iars2 Hspa13 Eif4a2 Eif3f Rnf149 Eif2b1 Prmt5 Smurf2 Fbxo42 Usp18 Tars2 Eif4a2 Eif3f Fbxl5 Rnf149 Btbd9 Hspb8 Fkbp1a Eif2b1 Prmt5 Ndufaf1 Rps6 Fbxo42 Tars2 Fkbp3 Farsb Fkbp1a Eif4a1Eif4a1 Ndufaf1 Rps6 Fbxl5 Btbd9 Rce1Rce1 SclyScly Iars Farsb Nars Hspb8 Fkbp3 MrMrplpl33 Iars Nars Eif2b3 Rnf152 Socs4 Tmed5 Abcg2 Eif2b3 Rnf152 Socs4 Rars Tmed5 Derl2 Abcg2 Zbtb6 Rars Derl2 Sdhaf1 Zbtb6 Rnf166 Polr2f Nr3c1 Eif3e Sdhaf1 Rnf166 Abhd5 Ctso Polr2f Bhmt Nr3c1 Eif3e Rnf139 Abhd5 Ctso Haao Bhmt Tmlhe Gm10094 Atpaf2 Rnf139 Socs2 Haao Tmlhe Tmem70 Mib1 Socs2 Gm10094 Atpaf2 Tmem70 Mib1 SrSrp6p688 Rars2 Txn2 Chfr Rnf135 Rars2 Mars Gypc Rpl32 Fbxl6 Txn2 Kars Foxred1 Chfr Rnf135 Mars Gypc Rpl32 Fbxl6 Srd5a1 Foxred1 Mrpl23 Kars Tcp1 Srd5a1 Mrps6 Mrpl23 Btbd7 Tcp1 Mrps6 Rnf167 Ncl Il17ra F7 Snupn Rnf167 Btbd7 Bbox1 Ncl Capn2 Il17ra F7 Snupn Fbxl8 Srpr Bbox1 Capn2 Polr2g Acin1 Clns1a Fbxl8 Srpr Rsl1d1 Eif4ebp1 Acin1 Clns1a Rnf138 Polr2g Rsl1d1 Ufd1l Il17rb Rab34 Eif4ebp1 COX1 Rnf138 Ufd1l Rabl2 Rab34 Eif3g Rnf146 Il17rb COX1 Wdtc1 Cndp2 Rabl2 Sap18 Eif3g Rnf146 Farsa Rab32 Rnps1 Sap18 Mrpl20 Mkrn2 Wdtc1 Aldh5a1 Cndp2 Farsa Fkbp2 Rnps1 Mkrn2 Uqcrh Rab32 Samm50 Tomm5 Mrpl20 Uqcrh Aldh5a1 Fkbp2 Edc4 Nsfl1cNsfl1c Rabl3 Eif2s2 Samm50 Tomm5 Usp16 Ppib Edc4 Tnfrsf12a Rabl3 Rab17 Eif2s2 Asb8 Usp16 Ppib Tnfrsf12a Rab17 Nup35 Tefm Mrpl22 Asb8 Mkrn1 Sars Ddx6 Rnd2 Nup35 Mrpl22 Sars Ddx6 Tefm Mkrn1 Fars2 Dars Rnd2 Smn1 Fars2 Dars Nploc4 Smn1 Ppid Rab12 Dcaf7 Ppid Nploc4 Rab12 Dcaf7 Srp19 Polr2i Rab29 Eif4e Cish Srp19 Polr2i Noc2l Tram1 Rab29 Eif4e Srrm1 Nubpl Mrpl32 Senp5 Cish Atp5b Eef1e1 Noc2l Tram1 Cyfip1 Srrm1 Nubpl Mrpl32 Senp5 Atp5b Eef1e1 Arf4 Cyfip1 Fbxw9 H13 Arf4 Rab39Rab39 Rpl30 Fbxw9 H13 Vars Arf3 Eif3d Usp14 Abhd14b Vars Arf3 Eif3a Eif3d Usp34 Btbd1 Usp14 Abhd14b Sars2 Eif3a Usp34 Btbd1 Polr2l Sepsecs Sars2 Ang Elac2 Phax Srp54a Polr2l Nfs1 Sepsecs Ang Elac2 Phax Rpl29 Srp54a Nfs1 Dhx36 Ivd Dhx36 Eif4g3 Rpl29 Btbd6 Ivd Nop2 Rab6a Xrcc6bp1 Btbd6 Nop2 Arl13b Rab6a Eif4g3 Tomm22 Xrcc6bp1 Rpl35 Btbd2 Arl13b Eif4e2 Tomm22 Rpl35 Senp6 Btbd2 Rrp12 Mrpl19 Senp6 Tr im2 Eif4e2 Mrpl19 Tr im2 Srp54b Rrp12 Thoc7 Kdm2a Srp54b Polr2d Rhoc Eif3i Kdm2a Polr2d Pabpc1 Rab18 Rhoc Sumo1 Thoc7 Eif3i Tomm6 Pabpc1 Arf5 Rab18 Sumo1 Ggt6 Polr3e Aars2 Tomm6 Dcaf8 Aars2 Arf5 Usp36 Ggt6 Polr3e Lsm8 Rab28 Cbll1 Ubr7 Dcaf8 Vars2 Lsm8 Gnb2l1 Rab28 Usp36 Cbll1 Rnd1 Ubr7 Vars2 Gnb2l1 Rhob Rnd1 Rit1 Sumo2 Rit1 Rhob Rab4b Sumo2 Fxr1 Eif3j1 Bfar Bpnt1 Rab4b Fxr1 Rnf216 Traf7 Aars Eif4g2 Eif3j2 Eif3j1 Rnf217 Bfar Bpnt1 Rnf216 Traf7 Aars Trmt112 Eif4g2 Eif3j2 Rnf217 Polr1d Rtcb Rplp1 Polr1d Trmt112 Rtcb Rab43 Gnat1 Fxr2 Rplp1 Usp46 Rab43 Gnat1 Fxr2 Usp46 Rnd3 Usp12 Polr1c Sumo3 Eif4g1 Mycbp2 Mul1 Fbxw5 Usp12 Sppl2a Polr1c Rnd3 Sumo3 Eif4a3 Eif5 Eif4g1 Eif3b Mycbp2 Mul1 Fbxw5 Sppl2a Lactb Vcp Fmr1 Eif3b Acad9 Rap2c Lactb Fmr1 Eif4a3 Fbxw4 Vcp Rap2c Tr nt1 Acad9 Ift27 Tr nt1 Tomm7 Zbtb9 Fbxw4 Polr2e Aimp2 F2 Arl1 Ift27 Timm50 Tomm7 Zbtb9 Polr2e Aimp2 F2 Arl1 Timm50 Mrpl36 Eif5b Mrpl36 Rpl19 Usp10 Polr2a Eif1ax Eif5b Usp10 Polr3k Rab35 Eif2s1 Rpl19 Rnf170 Polr2a Arl5a Nkiras1 Eif1ax Rnf170 Polr3k Rnaset2b Lamtor5 Arl5a Nkiras1 Rab24 Rab35 Eif2s1 Fbxw2 Rnaset2b Lamtor5 Rab24 Nup214 Fbxw2 Polr3c Abat Aimp1 Asrgl1 Nup214 Polr3c Polr3d Aimp1 Polr3b Abat Ipo8 Rae1 Asrgl1 Ipo8 Thoc6 Rae1 Eif1a Mysm1 Abhd14a Polr3b Polr3d Larp1b Thoc6 Eif1a Mysm1 Abhd14a Polr2j Polr1a Rap2a Nkiras2 Arfrp1 Larp1b Timm17b Polr1a Rap2a Nkiras2 Arfrp1 Timm17b Letm1 Polr2j Nsun2 Faf2 Letm1 Mrps25 Rps9 Nsun2 Lrp1 Faf2 Seh1l Strap Timm17a Mrps25 Rps9 Lrp1 Anp32b Seh1l Strap Timm17a Polr3h Polr3g Arl4d Rpl21 Polr3h Polr3g Hnrnpul1 Rhod Anp32b Arl4d Eif3c Rpl21 Hnrnpul1 Rhod Eif3c Diablo Ndufaf4 Taf13 Ivns1abp Larp1 Diablo Rps10 Pin1 Taf13 Polr3f Ndufaf4 Ivns1abp Agfg1 Larp1 Ndufaf6 Rps10 Pin1 Polr3f Skiv2l2 Fbxo6 Agfg1 Arl8b Ndufaf6 Ndufaf7 Skiv2l2 Fbxo6 Arl8b Rab21 Ndufaf5 Ndufaf7 Taf11 Sephs2 Rab20 Rab21 Ndufaf5 Tmem126b Ufc1 Taf11 Sephs2 Kpna2 Rab20 Tmem126b Ufc1 Rnf130 Kpna2 Eri1 Usp40 Rnf130 Tnrc6b Mrps26 Rpl22l1 Usp40 Afmid Pdia4 Plg Arl8a Dcp2 Tnrc6b Eri1 Mov10 Rpl22l1 Taf6 Furin Arl4a Dcp2 Mrps26 Mrps9 Gtf2b Afmid Pdia4 Plg Arl8a Mov10 Apobec1 Hemk1 Taf6 Furin Arl4a Mrps9 Gtf2b Apobec1 Lsm14b Hemk1 Mtrf1 Ift22 Lsm14b Mtrf1 Dcaf12 Ift22 MrrfMrrf Dcaf12 Eif4enif1 Zfp36 Pnrc2 Gtf2i Arl5b Eif4enif1 Pnrc2 Smg9 Gtf2i Hgd Derl1 Zfp36 Cpn1 Arl5b Smg9 Hgd Derl1 Kpna1 Cpn1 Tnrc6a Tnpo1 Mtrf1l Mrps27 Kpna1 Atp6v1d Tnrc6a Tnpo1 Ccrn4l Abcf1 Mtrf1l Gtf2h5 Atp6v1d Ccrn4l Abcf1 Mrps27 Gtf2h5 C1qbC1qbpp Rab30 Asb13 Rab30 Gps1 Gtf2ird1 Taf12 Sephs1 Mocs3 Srpk1 Als2 Eef1b2 Asb13 Gps1 Dcun1d5 Gtf2ird1 Taf10 Srpk1 Cox7b Cluh Dcun1d5 Taf10 Taf12 Sephs1 Mocs3 Als2 Cox7b Cluh Eef1b2 Josd2 Gtf2e2 Dcps Tnrc6c Mrpl43 Josd2 Tbp Gtf2e2 Dcps Tnrc6c Mrpl43 Tbp Atp5f1 D19Bwg1357e Fastk Tr im44 Trim33 D19Bwg1357e Fastk Tr im44 Ubc Trim33 Taf2 Atp5f1 Fbxl13 Ubc Taf2 Fbxl13 Taf5l Nags Mrpl33 Josd1 Taf5l Nags Mrpl33 CopsCops22 Josd1 Gabbr2 Kmt2d Hspa9 Gtf2h4 Gabbr2 Ercc3 Kmt2d Wdr61 Hspa9 Irf9 Gtf2h4 Irf9 Ercc3 Wdr61 Park7 Ptrh2 Zbtb16 Usp9x Te ad1 Zfp36l1 Abcf3 Usp9x Te ad1 Gtf2a2 Gltscr2 Park7 Zfp36l1 Ptrh2 Abcf3 Zbtb16 Gtf2a2 Dnajc3 Gltscr2 Cetn3 Usp24 Dnajc3 Cetn3 Rpl22 Usp24 TaTaf1f155 Gtf2f1 Copa Rnf128 Cdk7 Gtf2f1 Tst Copa Rpl22 Rnf128 Irf7 Tst Irf7 Cdk7 Rplp2 Dcaf10 Auh Rplp2 Rnf187 Dcaf10 Irf5 Tha1 Oat Auh Gpt2 Gle1 Cops3 Rnf187 Irf5 Tha1 Sat2 Gpt2 Ddx3x Taf3 Oat Gle1 Eef1g Mpst Tspo Dhx40 Ddx3x Eef1g Cops3 Taf3 Sat2 Mpst Bcap31 Crtc3 Atp5k Rnase4 Klf13 Dhx40 Bcap31 Tspo Usp32 Crtc3 Atp5k Rnase4 Rcc1 Zbtb17 Klf13 Acy1 Rcc1 Zbtb17 Usp32 Irf1 Ccnh Acy1 Eef1d Med8 Ubd Lnx2 Klf1 Med8 Ndufa10 Papd4 Ubd Irf1 Klf1 Ccnh Eef1d Nedd8 Lnx2 Siah2 Zranb1 Hivep1 Gtf2h2 Ndufa10 Papd4 Irf2 Gtf2h1 Rps20 Siah2 Zranb1 Hivep1 Gtf2h2 Rpl27a Klhl5 Nedd8 Rnf31 Relb Rps20 Fbxo34 Irf2 Gtf2h1Gtf2f2 Rpl27a Klhl5 Rnf31 Fbxo33 Relb Atp5a1 Fbxo34 Tbx3 Gtf2f2 Sar1a Fbxo33 Atp5a1 Ndufb3 Tbx3 Sar1a Ndufb3 Myo5b Klf6 Thra Gtf2h3 Vac14 Myo5b Rps8 Thra Klf9 Klf6 Gtf2h3 Vac14 Tufm Arnt Rps8 Klf9 Klf7 Tufm Usp48 Arnt Taf1 Atp6v1c1 Zyg11b Usp47 Klf7 Gps2 Atp6v1c1 Usp48 Zyg11b Usp47 Foxa2 Taf1 Ifit1 Gps2 Sarnp Tr im7 Foxa2 Taf7 Sarnp Tr im7 Gabpa Ifit1 Rnf125 Gabpa Taf7 Sel1l Ero1lb Htra2 Fbxl15 Rnf125 Gpt Sel1l Ero1lb Hcfc2 Htra2 Fbxl15 Mnat1 Gpt Hcfc2 Hcfc1 Ranbp3 Ndufa2 Klf10 Mnat1 Hcfc1 Ccs Klf10 Esrra Hsf1 Ranbp3 Ndufa2 Ccs Mdm4 Esrra Hsf1 Anp32a Pja2 Mdm4 Foxa3 Tomm40 Anp32a Pja2 Foxa3 Foxa1 Sar1b Snd1 Tomm40 Ndufa1 Foxa1 Irf6 Nr2f6 Sar1b Snd1 Nrf1 Ago2 Ago1 Irf6 Nr2f6 Ufm1 Zfhx4 Tr p53inp1 Nrf1 Ago2 Ago1 Ufm1 Zfhx4 Tr p53inp1 Lhpp Esr1 Lhpp Ago3 Mrps31 Foxn3 Esr1 Rab9 Tomm40l Shpk Ago3 Mrps31 Foxn3 Klf15 Nfix Got1 Ranbp1 Rab9 Tomm40l Shpk Larp4 Klf15 Nfix Got1 Ranbp1 Ndufv3 Larp4 Foxn2 Ntn3 Fam103a1 Rps15a Plxna2 Ablim1 Ndufv3 Rel Foxn2 Tfam Fam103a1 Pja1 Ero1l Ntn3 Rps15a Thrb Plxna2 Ablim1 Zfhx3 Tfam Etv6Etv6 Ngef Pja1 Rel Thrb Zfhx3 Ero1l Lyn Ngef Dcaf11 Fosl2 Hif1a Lyn Efnb1 Ubr3 Dcaf11 Fosl2 Hif1a Efnb1 Ubr3 P4hb Jak2 P4hb Ict1 Jak2 Nrp1 Ndufb6 Larp4b Ict1 Mrpl40 Ar E2f1 Ar E2f1 Atf4 Nfkbia Nrp1 Ndufb6 Larp4b Mrpl40 Mrps30 Epas1 Rcor1 Mrps10 Nfkbib Atf4 Nfkbia Sema4a Dap3 Mrps30 Epas1 Tdo2 Rhog Arhgef26 Cd2ap Rcor1 Sema4a Plxnb2 Mrps10 Dap3 Zfand4 Hectd1 Nfkbib Tdo2 Ptma Rhog Arhgef26 Cd2ap Tgm2 Plxnb2 Mrps28 Trim47 Zfand4 Hectd1 Ptma Tgm2 Atp6v1e1 Atp6v1a Hax1 Mrps28 Klhl2 Trim47 Clock Htt Atp6v1e1 Hax1 Ubr2 Igtp Htt Atp6v1a MrMrpl21pl21 Klhl2 Ubr2 Clock Igtp Atp6v1b2 PaPak1ip1k1ip1 Nfib Atp6v1b2 Ddx19b Dis3l Atf5Atf5 Nfic Nfib Erp29 Sema4gSema4g Ddx19b Dis3l Zbtb20 TrTrimim88 Usp5 Nfx1 Atf3 Nfic Erp29 Tlr5 Wasl Zbtb24 Usp5 Nfx1 Zbtb20 Atf3 Nr2c1 Tlr5 Hc Wasl Eif3m Rpsa Zbtb24 Rc3h1 Tr im56 Zbp1 Eif3m Tr im26 Jun Nr2c1 Hc Cpeb2 Cpeb4 Rc3h1 Tr im56 Guca1a Rpsa Peli2 Zbp1 Tr im26 E2f3 Jun Guca1a Cpeb2 Cpeb4 Gigyf2 Rnf2 Peli2 Cdk5 Rnf19b Kbtbd4 E2f3 Nr2c2 Nr2f2 Maob Srgap2 Gigyf2 Rnf2 Cdk5 Fbxl17 Rc3h2 Rnf19b Kbtbd4 Nr2c2 Nr2f2 Maob Srgap2 Angel2 Angel2 Fbxl17 Rc3h2 Peli1 Ppa2 G3bp1 Eef1a1 Mrpl41 Ring1 Peli1 Tr im11 Rbbp6 Mtf2 Ppa2 Sqstm1 Ring1 G3bp1 Eef1a1 Ddx24 Tr im11 Rbbp6 Tr im28 Tfdp2 Mtf2 Sqstm1 Mrpl41 Irf3 Gigyf1 Ddx24 Tr im28 Ndufb11 Gigyf1 Tfdp2 Irf3 Ndufb11 Ebna1bp2 Mrpl42 Cops8 Egr1 Dis3l2 Mrpl42 Cops8 Nfil3 Egr1 Atp5e Zbtb38 Rock1 Dis3l2 Ebna1bp2 Gan Ubb Rnf40 Nfil3 Nfia Atp5e Zbtb38 Rock1 Gan Rnf40 Fos Nfia Herpud1 Stau1 Ubb Atp6v1g1 Ttc3 Uhrf2 Fos Zfhx2 Herpud1 Caprin1 Stau1 Hp Atp6v1g1 Tut1 Ttc3 Uhrf2 Cbx4 Hp Zfhx2 Cox6a1 Caprin1 Tut1 Rnf20 Fbxo31 Cbx4 Rock2 Cox6a1 Klhl12 Znrf2 Rnf20 Fbxo31 Rock2 Klhl12 Znrf2 Dcun1d1 Spsb2 Dcun1d1 Ndufb2 Bccip Ddx21 Zbtb33 Spsb2 Arntl Ndufb2 Bccip Ddx21 Zbtb33 Rnf19a Vcpip1 Junb Arntl Amfr Bop1 Rnf19a Vcpip1 Junb Amfr Eif2a Tmed7 Bop1 Id2 Znrf1 Tmed7 Mrpl52 Hltf Ahr Eif2a Id2 Stat3 Eef2 Topors Znrf1 Csrp2 Mrpl52 Tmx3 Hltf Uba5 Bcl3 Ahr Csrp2 Stat3 Eef2 Topors Rnf14 Ppan Mrps34 Tmx3 Ccnf Uba5 Bcl3 Tdrd3 Ppan Mrps34 Ccnf Rnf14 Jund Tdrd3 Pdia5 Jund Exosc4 Eif3Eif3ll Pdia5 Wsb1 Rxrb Ndufa3 Exosc4 Wsb2 Dcaf5 Pigr Adrbk1 Ddx51 Fkbp15 Wsb1 Tr im14 E2f8 Rxrb Ndufa3 Wsb2 Dcaf5 Pigr Adrbk1 Cox6c Ddx51 Tma16 Fkbp15 Tr im14 Tr im27 Usp4 E2f8 Nfe2l2 Tr im27 Usp4 Nfe2l2 Cox6c Tma16 Tpp2 Mafb Tshz1 Ndufb5 Stat1 Stat1 Tmed5 Tpp2 Mafb Tshz1 Csrp3 Ndufb5 C9 Wdr12 Tmed5 Nop9 Rbm19 Ftsj3 Spsb3 Csrp3 Shpk C9 Pxn Wdr12 Nop9 Rbm19 Ftsj3 Zfp593 Spsb3 Hectd3 Rbck1 Gabpb2 Shpk Hectd3 Rbck1 Gabpb2 Pxn Zfp593 Bag5 Rnf123 Nfatc3 Tshz2 Etv3 Cyld Pdcd2l Bag5 Rnf123 Usp15 Bach1 Etv3 Cyld Ndufa6 Pdcd2l Spsb4 Usp15 Usp3 Nfatc3 Bach1 Tshz2 Ndufa6 Spsb4 Usp3 Ppa1 Amdhd1 Stat2 Ubr1 Dbp Amdhd1 E2f6 Ppa1 Dbp Hspd1 Stat2 Cebpz St13 Ubr1 Yy1 Rab40c Mrps15 Zbtb43 Rnf115 E2f6 Hspd1 Atp6v0d1 Cebpz St13 Pparg Tef Yy1Hmga1- Rab40c Rnf11 Uqcr11 Mrps15 Zbtb43 Abtb1 Cebpg Atp6v0d1 Rnf11 Rnf115 Pparg Tef Hmga1- Uqcr11 Abtb1 Nfkbiz Cebpg Fbxo3 rs1 Pinx1 Atp8a2 Sdad1 Fbxo3 Rlim Fbxo9 Zbtb48 Nfkbiz rs1 Pinx1 Ddx10 Pdcd2 Atp8a2 Sdad1 Rlim Fbxo9 Zbtb48 Rnf126 Rnf121 Got2 Ddx10 Pdcd2 Arih1 Rnf126 Rnf121 Got2 Arih1 Brwd1 Id3 Elf2 Mat2a Gars Mrpl51 Chordc1 Brwd1 Id3 Elf1 Elf2 Mat2a Gars Mrpl51 Mrps33 Chordc1 Rnf13 Phip Elf1 Bre Rb1 Tex10 Ankib1 Mrps33 Bag3 Bre Rnf13 Phip Rb1 Ddx47 Tex10 Bag3 Pcsk9 Ankib1 Mxi1 Lyar Ddx47 Pcsk9 Arih2 Brwd3 Xbp1 Mxi1 Elk4 Maoa Cct8 Elk4 Lyar Wdr18 Rrs1 Hscb Arih2 Brwd3 Xbp1 Maoa Nip7 Wdr18 Rrs1 Hscb Cct8 Lrrc41 Pars2 Wars Ya rs2 Nip7 Ccdc86 Lrrc41 Eif2d Pars2 Wars Ya rs2 Rsl1d1 Ncl Mat2b Ndufs1 Eif2d Rsl1d1 Ncl Ccdc86 Brcc3 Fbxo7 Uchl3 Mat2b Ndufs1 Brcc3 Fbxo7 Uchl3 Inhba FbxoFbxo88 Mxd4 Mak16 Rrp8 Mrpl45 Inhbe Inhba Zbtb44 Rnf114 Mxd4 Atp5h Mak16 Nol12 Rrp8 Mrpl44 Mrpl45 Inhbe Zbtb44 Rnf114 Atp5h Nol12 Mrpl44 Uchl4 Nop14 Krr1 Uchl4 Tr pc4ap Hlf Nop14 Krr1 Pno1 Rpf2 Dnajb4 Uchl5 Tr pc4ap Hlf Ya rs Pno1 Rpf2 Dnajb4 Otub1 Uchl5 Serpind1 Ya rs Tsr3 Shq1 Otub1 Cars2 Tsr3 Shq1 Serpind1 Cars2 Cars Tars2 Nsun5 Ubac1 Rnf41 PparPparaa Elf3 Cars Tars2 Nop2 Ubac1 Rnf41 Elf3 Nsun5 Nop2 Ngdn Kri1 Klhl22 Eif5a Las1l Clpx Klhl22 Fbxo28 Atoh8 Atf6 Ngdn Kri1 Afg3l2 Rnf26 Eif5a Tars Las1l Clpx Fbxo28 Atoh8 Cnbp Atf6 Tars Rrp1b Afg3l2 Rnf26 Sp5 Arg1 Ftsj2 Cnbp Tcirg1 Mrto4 Rrp1b Otud5 Klhl24 Trim24 Sp5 Arg1 Utp3 Brix1 Ftsj2 Ybx1 Tcirg1 Pwp1 Lars Tfb1m Utp3 Brix1 Mrto4 Cops4 Otud5 Klhl24 Trim24 Bmyc Zbtb7a Ybx1 Eif3k Lars Pwp1 Ddx49 Bmyc Eif3k Tfb1m Ddx49 Inhbc Cops4 Tr im17 Rnf111 Rxra Zbtb7a Hsp90b1 Ears2 Inhbc Klhl21 Otud7b Tr im17 Rnf111 Rxra Atp6v0a1 Hsp90b1 Gatc Klhl21 Cops6 Otud7b Atp6v0a1 Ears2 Lman1 Gatc Ddx56 Tsr2 Cops6 Abt1 Ltv1 Capns1 Nr5a2 Lman1 Ddx56 Tsr2 Ltv1 Serpinc1 Noc4l Abt1 Rrp1 Klhl25 Rnf43 Capns1 Nr5a2 Ndufs2 Noc4l Rrp1 Klhl25 Rnf43 Dcaf6 Zbtb7c Zbtb7b Ssr1 Serpinc1 Wdr46 Ndufs2 Hars Utp20 Dcaf6 Cul9 Nfe2l1 Zbtb7c Zbtb7b Ssr1 Wdr46 Ubp1 Hars Utp20 Cul9 Nfe2l1 Lars2 Ddx54 Ubp1 Clk2 Lars2 Ddx54 Ddx52 Dusp12 Bap1 Cebpa Aebp2 Clk2 Iars2 Gatb Nsa2 Tsr1 Dusp12 Bap1 Crbn Rora Cebpa Aebp2 Iars2 Gatb Noc2l Ddx52 Nsa2 Utp23 Tsr1 Grwd1 Usp1 Crbn Rora Peg3 Noc2l Ddx55 Pdcd11 Utp23 Grwd1 Usp1 Ebf1 Rxrg Peg3 Taf15 Ndufb10 Ndufa4 Ddx55 Pdcd11 Cops5 Rest Ebf1 Rxrg Zscan22 Clk1 Taf15 Ndufb10 Hars2 Fbxo22 Rest Zscan22 Clk1 Ndufa4 Rrp9 Cops5 Cpd Zkscan1 Rexo4 Atp5d Qars Hars2 Rrp9 Fbxo22 Rhbdd2 Nol9 Rexo4 Cpd Nr0b2 Zkscan1 Atp5d Qars Farsb Noc3l Rhbdd2 Dph5 Iars Nol9 Nr0b2 Dph5 Iars Farsb Noc3l Rbm34 Zfp444 Clk4 Rbm34 Dnajc18 Usf1 Sp3 Zscan21 Clk4 Bysl Dnajc18 Dda1 Usf1 Sp3 Zfp444 Esd Atp5j Zscan21 Atp5j Dnajc24 Vars Bysl Mtg2 Dda1 Esd Ndufa11 Ppme1 Dnajc24 Vars Nifk Aatf Zfp622 Mtg2 Rnf103 Srebf1 Ndufa11 Ppme1 Zscan26 Ndufs8 Dus3l Nifk Aatf Zfp622 Rnf103 Srebf1 Zfp445 Ndufs8 Dus3l Abcf2 Otud6b Usf2 Zkscan3 Zfp445 Zscan26 Clk3 Rrp36 Wdr74 Zfp191 Kars Abcf2 Rrp36 Otud6b Otulin Usf2 Zkscan3 Zfp191 Clk3 Rars Kars Wdr74 Otulin Fbxo21 Dnajc10 Pou2f1 Isca1 Dnajc10 Pou2f1 Rars Nars Isca1 Fbxo21 Cox5a Nars Cops7a Zfp213 Prpf4b Cox5a Fars2 Klhl28 Zfp213 Zbtb5 Prpf4b Fars2 Cops7a Klhl28 Eif2ak1 Zbtb5 Rars2 Utp11l Rpf1 Eif2ak1 Ahrr Rpf1 Slc25a21 Rars2 Dars Trmt11 Utp11l Ahrr Dars Vprbp Nr1i2 Slc25a21 Inmt Uggt1 Dnajc21 Atp5g2 Farsa Dars2 Trmt11 Dcaf13 Vprbp Nr1i2 Ubtf Inmt Uggt1 Dnajc21 Prkcsh Atp5g2 Farsa Dars2 2700060E02Rik Dph3 Dcaf13 Svip Ssrp1 Ubtf Dnajc8 Prkcsh 2700060E02Rik Tr mt112 Dph3 Svip Ssrp1 CxxcCxxc11 Dnajc8 Slc25a16 Nars2 Tr mt112 Usp2 Rorc Slc25a16 Nars2 Usp2 Ipp Spop Rorc Glyctk Ipp Spop Atrx Tcf7l1 Mat1a Glyctk Pes1 Atrx Tcf7l1 Mat1a Cnbp Tcf3 Ccdc55 Elp4 Pes1 Tcf3 Rnpc3 Ccdc55 Cnbp Sepsecs Pstk Elp4 Creb3l3 Rnpc3 Pstk Khdrbs1 Sepsecs Adat3 Elp3 Creb3l3 Adat3 Elp3 Isg20 Cux1 Khdrbs1 Zfp790 Aars Isg20 Tnfaip1 Cux1 Zfp790 Aars Mars Tr mt12 Bpnt1 Tnfaip1 Mars Tr mt12 Dus2 Ang4 Bpnt1 Mef2a Olig1 Preb Snrpf Dus2 Dus1l Ang4 Hsp90aa1 Mef2a Olig1 Preb Snrpf Tyw3 Dus1l Derl2 Ahcy Hsp90aa1 Hhex Tyw3 Derl2 Ahcy Sf1 Ybx1 Tyw1 Dtd1 Cpb2 Hhex Wdr83 Mbnl1 Sf1 Ybx1 Tyw1 Rpp21 Dtd1 Zcchc7 Cpb2 Wdr83 MbnlSn1rnp48 Os9 Rpp21 Zcchc7 Adam9 Bhlhe40 HnHnrrnnpa2bpa2b11 Snrnp48 Hyou1 Os9 Elp2 Adam9 Bhlhe40 Hyou1 Ndufs4 Aars2 Mettl1 Dnaja2 Aars2 Elp2 Vimp Dnaja2 Ndufs4 Tr mt1 Eef1e1 Mettl1 Cct7 Vimp Mbnl2 Eef1e1 Ssr4 Mbnl2 Tr mt1 Cct7 Cox5b Tsen15 Ssr4 Nfat5 Nosip Cox5b Sars Tsen15 Nfat5 Nosip Ssrp1 Sars SsrpUbtf1 Derl3 Wfs1 Creb3 Otc Ubtf Lage3 Calr Nsfl1c Wfs1 Creb3 Dhx9 Derl3 Otc Gtpbp3 Lage3 Calr Nsfl1c Dhx9 Ddx18 Mcee Nr1h3 Ddx18 Mcee Ndufa9a9 Gtpbp3 Rnaset2b Nr1h3 Tfe3 Ssr3 Rnaset2b Tfe3 Ssr3 C6 Rtcb Atf6Atf6bb Hnrnpf C6 Sars2 Tr mt2a Rtcb Hes1 Snrpf Hnrnpf Sars2 Tr mt2a Tsen34 Hes1 Snrpf Ddx3Ddx399 Tsen34 Tcf12 Ide Aimp2 Tcf12 Sugp1 Hnrnpf Fam50aSnrnp35 Ide Lcmt2 Hnrnpf Fam50a Lcmt2 Aimp2 Sugp1 Sf1 Snrnp35 Sec23b Dnajb6 Kmt2a Sf1 Ddx50 Acad8 Sec23b Dnajb6 Dnajc13 Fam98b Tprkb Kmt2a Ddx50 Acad8 Pdia3 Canx Dnajc13 Rab8a Fam98b Tprkb Pdia3 Canx Tcf4 Srm Rab8a Atp5g1 Mto1 Rpp14 Srm Atp5g1 Mto1 Rpp14 Tcf4 Kmt2e Dpf2 Nr1h4 Kmt2e Dpf2 Ube2g2 Hnrnph1 Nr1h4 Raly Ube2g2 Hnrnph1 Prodh2 Cyc1 Tyw5 Rnaset2a Rbm5 Raly Khdrbs3 Prodh2 Cyc1 Tyw5 Amt Rnaset2a Tfeb Bcas2 Rbm10 Rbm5 Khdrbs3 Amt Tram1 Foxk2 Bcas2 Qtrt1 Tnpo3 Tfeb Rbm10 Sil1 Hnrnph2 Tram1 Foxk2 Ndufa7 Qtrt1 Tnpo3 Hspb6 Dnajc15 Skp1a Nr1i3 Snrpg Sil1 Sec23a Hnrnph2 Dhx9 Ndufa7 Hspb6 Dnajc15 Skp1a Pbx1 Nr1i3 Snrpg Sec23a Dhx9 Pbx1 Ftsj1 Sox6 Celf2 Prodh Ftsj1 Sox6 Celf2 Prodh Vcp Foxo3 Hnrnpdl Qk Slc25a1 Shmt1 Hnrnph1 Vcp Foxo3 Hnrnpdl Qk Slc25a1 Shmt1 Hnrnph1 Osgep Tr p53 Kmt2c Sox5 Snrpd1 Dnajb11 NsunNsun22 Osgep Tr p53 Kmt2c Sox5 Snrpd1 Dnajb11 Srebf2 Rbm39 Bcap31 Srebf2 Ppih Celf1 Rbm39 Bcap31 Zfp949 Ppih Ctnnbl1 Hnrnpm Celf1 Ufd1l Zfp949 Ctnnbl1 Hnrnpm Snrpg Snrnp70 Atp5j2 Tr mt6 Ufd1l Zfp612 Zfp398 Nr1h2 Snrnp70 Aimp1 Nr1h2 Snrpg Serpina1a Atp5j2 Aimp1 Tr mt6 Zfp612 Zfp560 Zfp398 Hes6 Hsp90ab1 Zfp560 Serpina1a Scyl1 Hsp90ab1 Hes6 Ddx27 Ddx27 Scyl1 Wdr4 Atxn3 Ppie C8a Wdr4 Atxn3 Zfp110 Ppie Hnrnpd Cox6b1 C8a Rnf185 Zfp110 Hnrnpd Cox6b1 Snrnp70 Ptcd1 Dnajc12 Rnf185 Rnf5 Ddx17 Tr mt2b Zfp426 Snrnp70 Pdia6 Ptcd1 Dnajc12 Rnf5 Ddx17 Tr mt2b Zfp426 Sox9 Pdia6 Nploc4 Hnrnpab Atp5g3 Nploc4 Sox9 Pqbp1 Hnrnpab Ppia Stip1 Gm6710 Pqbp1 Lman2 Ndufa8 Atp5g3 Fbxo6 Cirbp Gm6710 Cwc15 Smndc1 Hal Ppia Stip1 Dnajb2 Lman2 Ndufa8 Cirbp Fbxo6 Zfp746 Cwc15 Smndc1 Htatsf1 Hal Pus1 Sel1l Dnajb2 Zfp946 Glt25d1 Pus1 Sel1l Zfp746 Zfp946 Cd2bp2 Htatsf1 Glt25d1 Sephs2 Tsen2 Osgepl1 Zfp51 Zfp623 Cd2bp2 Atp6ap1 Ndufs7 Sephs2 Tsen2 Osgepl1 Zfp51 Zfp617 Zfp623 Cwc22 Fam32a Atp6ap1 Cwc22 Ndufs7 Tr pt1 Clu Zfp617 Gtf3a Zcrb1 Gm13152 Fam32a Tr pt1 Clu Zfp1 Gtf3a Zcrb1 P4hb Gm13152 Zfp1 Plrg1 Sec24b Pus10 Sar1a Zfp768 Slc25a15 Sec24b Capn2 Zfp688 Zfp871 Plrg1 Pus10 Sar1a Zfp768 Srsf10 Ddx3y Slc25a15 Capn2 Trub1 Dnajc11 Ern1 Zfp688 Zfp871 Hsf2 Srsf10 Ddx3y Trub1 Dnajc11 Ern1 Ide Hsf2 Cdc5l Hspa13 Ide Bag1 Zfp386 Zcchc8 Cdc5l Hspa13 Bag1 Zfp386 Zfp809 Zcchc8 Puf60 FrFrg1g1 Dnaja2 Zfp809 Zfp944 Puf60 Cdk11b Dgcr14 Slc7a2 Thumpd1 Pus7 Dnaja2 Zfp938 Zfp944 Hnrnpa0 Cdk11b Dgcr14 Sec24d Snrpd1 Thumpd1 Pus7 Zfp68 Zfp938 Hnrnpa0 Snrpb2 Slc7a2 Sec24d Snrpd1 Zfp68 Hnrnpl Snrpb2 Hnrnpm Hnrnpl Kin Gemin6 Zfp830 Hnrnpm Hnrnpll Gemin6 Slc9a3r1 Derl1 Kin Zfp830 Ftcd Hnrnpll Snrpa Slc9a3r1 Slc39a14 Derl1 Ftcd Enoph1 Sec24a Zfp53 Zfp707 Snrpa Slc39a14 Pcsk7 Zfp53 Zfp707 Enoph1 Sec24a Pcsk7 Sar1b Gata6 Sar1b Gata6 Zfp30 Pin4 Zfp30 Pcbp1 Prpf40a Fra10ac1 Ddx1 Hnrnpr Pcbp1 Prpf40a Fra10ac1 Pin4 Mef2d Ddx1 Zfp954 Hnrnpr Mef2d Srf Setdb1 Zfp954 Zfp825 Ddx46 Hibch Setdb1 Edem1 Srf Zfp825 Ddx46 Hibch Gemin7 Cct5 Ero1lb Edem1 Gemin7 Snrpa1 Cct5 Ero1lb Phf5a Snrpa1 Atp5l Cct4 Pcsk6 Phf5a Rrbp1 Dnajc1 Atp5l Cct4 Pcsk6 Zfp58 Dhx30 Ddx5 Rrbp1 Dnajc1 Trap1 Zfp58 Dhx30 Ddx42 Ddx5 Sec24c Trap1 Foxp1 Ddx42 Sec24c Atp5c1 Foxp1 Mitf Rbm25 Atp5c1 Mitf Hnrnpk Rbm25 Ilf3 Ddx41 Rbfox2 Ilf3 Shmt2 Edem2 Rbfox2 Ddx23 Hnrnpk Ddx41 Shmt2 Edem2 Foxq1 Ddx23 Wbp11 Txndc5 Amfr Foxq1 Foxp2 Wbp11 Ppil1 Txndc5 Amfr Foxp2 Syncrip Fubp1 Prpf19 Ppil1 Uqcr10 Syncrip Fubp1 Ints1 Prpf19 Uqcr10 Ndufab1 Ints1 Slc25a22 Ndufab1 Ppib Xab2 Slc25a22 Hnrnpa2b1 Pfdn6 Xab2 Grhpr Ppib Pfdn6 Paxbp1 Tra2a Dhx15 Slc25a11 Grhpr Hnrnpa2b1 Paxbp1 Tra2a Dhx15 Prdx6 Fkbp11 Dnajc3 Slc25a11 Prdx6 Atp5o Fkbp11 Dnajc3 Wbp4 Atp5o Wbp4 Ptbp3 U2surp Srsf10 Erp29 Ptbp3 Snrpc U2surp Arglu1 Srsf10 Erp29 Paf1 Snrpc Ilf2 Arglu1 Eif2ak4 Paf1 Ptbp1 Srpk2 Wdr77 Ilf2 Eif2ak4 Ptbp1 Srpk2 Wdr77 Strbp Tra2b Hnrnpc Nmnat1 Cct3 Strbp Tra2b Hnrnpc Nmnat1 Ddx46 Ubqln1 Cct3 Rbm22 Elavl1 Hsph1 Ddx46 Ubqln1 Rbm7 Rbm22 Elavl1 Hsph1 Serbp1 Bud13 Rbmxl1 Rbmx Prpf40a Ints3 Csad Pcsk5 Lman1 Rbm7 Nmnat3 Pdia4 Rbmxl1 Rbmx Prpf40a Serbp1 Bud13 Hspa8 Ints3 Ccdc130 Csad Pcsk5 Pdia4 Lman1 Nmnat3 Plrg1 Hspa8 Ccdc130 Cwc27 Zmat5 Plrg1 Ubxn6 Erlec1 Rbm15 Zmat2 Cwc27 Zmat5 Mri1 Ubxn6 Rtf1 Rbm15 Hnrnpll Erlec1 Rtf1 Zmat2 Sf3a1 Snrpe Mri1 Hnrnpll Atp6v0b Dnajc9 Lman2 Med21 Zfr Matr3 Srsf7 Aqr Sf3a1 Snrpe Plaa Atp6v0b Cct2Cct2 Dnajc9 Lman2 Med21 Zfr Matr3 Srsf7 Aqr Coil Plaa PcskPcsk44 Ccdc12 Coil Med27 Msl2 Tia1 Pcbp2 Ccdc12 Dhx38 Med27 Zfp326 Esrp2 Msl2 Nono Tia1 Pcbp2 Bclaf1 Dhx38 Slc39a7 Arid2 Zfp326 Esrp2 Nono Bclaf1 Slc39a7 Dnajc7 Arid2 Med31 U2af2 Dnajc7 Plaa Med31 U2af2 Coq3 Hnrnpu Ndufs6 Ints10 Aldh6a1 Coq3 Plaa Hnrnpu Ero1l Tial1 Ints10 Slc6a12 Aldh6a1 Ndufs6 Slc6a13 Ndufs3 Ero1l Ctr9 Tial1 Slc6a12 Slc6a13 Chdh Ndufs3 Ctr9 Srsf4 Crnkl1 Chdh Srsf4 Dnajb12 Gtf3c1 Crnkl1 Rbm4b Dnajb12 Gtf3c5 Nelfa Med19 Gtf3c1 Rbm4b Snw1 Ndufb4 Gtf3c5 Med19 Ints4 Ndufb4 Nelfa Luc7l2 Aar2 Ints4 Snw1 Glrx5 Ssr1Ssr1 Tada2b Med6 Luc7l2 Aar2 Rbm17 Sec31a Glrx5 Tada2b Med6 Msl1 Srsf5 Rbm17 Sec31a Cdc73 Msl1 Srsf5 Srrm2 Cdc73 Srrm2 Abcb8 Prpf4b Prkcsh Txnl4a Abcb8 Prpf4b Hspb8 Clpb Herpud1 Prkcsh Rbm27 Txnl4a Slc38a4 Gsr Herpud1 Ctdsp1 Supt3 Brf1 Rbm27 Rbm3 Slc38a4 Hspb8 Clpb Baz2a Srsf6 Gsr Brf1 Srsf11 Rbm3 Syf2 Uggt1 Baz2a Leo1 Ctdsp1 Supt3 Setx Srsf6 Hnrnpl Odc1 Uggt1 Leo1 Kat2a Setx Ints5 Srsf11 Syf2 Tcerg1 Hnrnpl Odc1 Kat2a Ints5 Slc25a12 Snip1 Tcerg1 Snrpd2 Slc25a12 Ctdsp2 Snip1 Cherp Snrpd2 Dnaja1 Ctdsp2 Kat2b Usp39 Dnaja1 Srek1 Cherp Glul Mkks Kat2b Srek1 Usp39 Glul Gss Txn1 Mkks Txn1 Sart1 Gss Hnrnpd Fkbp9Fkbp9 Smarca5 Bdp1 Iws1 Srsf1 Prpf38b Sart1 Adi1 Hnrnpd Pfdn5 Smarca5 Brf2 Bdp1 Iws1 Srsf1 Prpf38b Adi1 Khdrbs1 Prpf31 Mccc2 Coq7 Uqcrq Pfdn5 Nelfcd Brf2 Coq7 Cdc5l Khdrbs1 Kmo Prpf31 Mccc2 Uqcrq Nelfcd Cdc5l Cox5b Kmo Preb Sf3a3 Cox5b Preb Srsf9 Hnrnpa3 Sf3a3 Alas1 Hnrnpab Ssr2 Arid1a Med13l Scaf4 Srsf9 Hnrnpab Srsf2 U2af1l4 Hnrnpa3 Ppig Alas1 Ssr2 Arid1a Med13l Scaf4 Ints12 Nit2 Gtf3c6 Srsf2 U2af1l4 Ppig Cpsf3l Ints12 Nit2 Gtf3c6 Cpsf3l Pnisr Os9 Med13 Ik Snrnp40 Prpf38a Snrnp27 Pnisr Os9 Snapc2 Med13 Sfpq Ik Snrnp40 Prpf38a Snrnp27 Dhx8 Mlycd Snapc2 U2af1 Dhx8 Mlycd Tada3 Med7 Sfpq U2af1 Apip Tra2a Glrx2 Med7 Eftud2 Akap17b Gpx4 Tra2a Tada3 Ints8 Akap17b Cbx3 Cbs Apip Hnrnpa0 Glrx2 Eftud2 Gpx4 Slu7 Ints8 Cbx3 Cbs Snrpa Hnrnpa0 Scaf8 Prpf6 Snrpa Nelfb Pbrm1 Scaf8 Prpf6 Slu7 Tra2b Nelfb Pbrm1 Prpf8 Ints9 Ppil3 Slc25a13 Tra2b Med9 Rbm26 Prpf8 Snrnp200 Ints9 Ppil3 Ccng1 Slc25a13 Dnajc2 Rbm26 Snrpd3 Snrnp200 Ppcs Tcp1 Dnajc2 Ube2g2 Med9 Snrpd3 Ccng1 Ppcs Nelfa Syncrip Tcp1 Ube2g2 Ppil4 Nelfa Syncrip Khsrp Ints3 Ell Ppil4 Sfpq Ints3 Txn2 Ell Med10 Actl6a Srsf3 Sf3b2 Dhx16 Shisa5 Sfpq Khsrp U2surp Txn2 Med10 Actl6a Dhx16 Dnajc4 Ell2 Med15 Smarca4 Srsf3 Sf3b2 Ddx39b Shisa5 Gstz1 Lias U2surp Dnajc4 Glrx Hsp90b1 Ell2 Med15 Smarca4 Ddx39b Gstz1 Lias Glrx Hsp90b1 Pcbp1 Dnajb9Dnajb9 Abcc6 Pcbp1 Rbm39 Med30 Rbm39 Med22 Cd82 Abcc6 Mtap Med30 Perp Ddx5 Dmgdh Pfdn4 Ssr3 Ngly1 Med22 Sf3b4 Sf3b1 Cd82 Mtap Coasy Fubp1 Ddx5 Pfdn4 Ssr3 Eaf1 Sf3b1 Perp Ass1 Fubp1 Dmgdh Ngly1 Rprd1b Sf3b4 Coasy Eaf1 Ass1 Smarca2 Cdc40 Celf1 Aff4 Smarca2 Rprd1b Sf3b3 Sf3bSf3b55 Cdc40 Celf1 Pdia6 Aff4 EnEny2y2 SnSnrprpbb Sf3b3 Pdia6 Med24 Ubl5 Slk Sil1 Med24 Fkbp8 Pan3 Slk Ubl5 Nampt Hnrnpr Ppid Sil1 Irak2 Acp1 Fkbp8 Pan3 Smarce1 Lmna Bax Tsc2 Nampt Hnrnpr Ppid Sec23a Prpf18 Irak2 Acp1 Dnajb11 Smarce1 Lmna Bax Tsc2 Sec23a Prpf18 Srr PfdnPfdn22 Papd5 Dnajb11 Nelfe Prpf4 Ei24 Srr Papd5 Med4 Tfip11 Prpf4 Ei24 Nelfe Med28 Tcea1 Tfip11 Ddx17 Aox3 Med28 Med4 Tcea1 SmarcdSmarcd22 RalyDdx17 Aox3 Smu1 Slc25a20 Smarcd2 Serbp1 Raly Exosc3 Snapc5 Mepce Smarcc2 Smu1 Casp8 Slc25a20 Smarcd2 Serbp1 Dnajb14 Exosc3 Rab8Rab8aa Snapc5 Mepce Smarcc2 Prkar1a Casp8 Ddx23 Dnajb14 Sf3bSf3b66 Prkar1a Ddx23 Plod1 Dxo Orc6 Mfap1a Myh9 Anapc5 Steap3 Plod1 Lsm8 Dxo Mfap1a Myh9 Orc6 Hnrnpk Pfdn1 Steap3 Uqcrc1 Lsm8 Btaf1 Anapc5 Hnrnpk Pfdn1 Dnajb1 Phf5a Uqcrc1 Btaf1 Smarcc1 Ints7 Tjap1 Dnajb1 Phf5a Snrpb2 Zc3h18 Aox1 Nktr Med1 Smarcc1 Ints7 Tjap1 Exoc3 Snrpb2 Ddx3yZc3h18 Aox1 Nktr Med1 Chd1 Spty2d1 Mfap1b Thrap3 Exoc3 Ptbp1 Ddx3y Edc4 Chd1 Spty2d1 Mfap1b Thrap3 Rab13 Asl Dhx15 Dis3 Ptbp1 Edc4 Rab13 Dhx15 C1d Lsm7 Sec23b Dnajc5 Ints6 Slc22a18 Asl Dis3 Aldh5a1 C1d Lsm7 Sec23b Dnajc5 Smarcb1 Ints6 Arhgap5 Cdc16 Slc22a18 Cyp2a12 Aldh5a1 Med29 Cgn Abcc3 Atxn7 Smarcb1 Med25 Arhgap5 Cttn Cdc16 Cyp2a12 Cgn Med29 Med25 Vcl Exoc4 Cttn Abcc3 Ilf3 Cnot10 Atxn7 Exoc4 Prkar2a Ido2 Ptbp3 Hnrnpc Mbtps1 Btg3 Chd2 Vcl Prkar2a Ido2 Gsto1 Ilf3 Cnot10 Hnrnpc Bhmt Mbtps1 Supt6 Ptbp3 Fkbp3 Rqcd1 Btg3 Hspbp1 Hyou1 Chd2 Endog Gsto1 Ndufv2 Bhmt Supt6 Tjp2 Ddx42 Fkbp3 Rqcd1 Hspbp1 Yod1 Hyou1 Endog Ndufv2 Supt5 Tjp2 Ddx42 Yo d1 Supt5 Ivd Mpst Fkbp1a Rbmx Fkbp2 Sec24d Supt4a Dbt Ppil1 Ivd Mpst Fkbp1a Btg1 Vapa Rbmx CYTB Sec24a Sec24d Supt4a Dbt Ppil1 Fkbp2 Txndc5 CYTB Cnot1 Btg1 Sec24a Vapa Txndc5 Cnot1 TaTaf1f1dd Exosc1 Taf1c Rrn3 Actn4 Exosc1 Rab1 Taf1c Rrn3 Actn4 Tjp1 Sugt1 Prpf19 Tst Tob2 Rab1 Tjp1 Sugt1 Aqp9 Prpf19 Tst Tob2 Sec24c Larp7 Ybx3 Fadd Aqp9 Rbm25 Sec24c Brd4 Larp7 Parva Ybx3 Fadd Rbm25Ddx1 Dcps Btg2 Lsm6 Brd4 Skil Parva Myl12a Ye s1 Ddx1 Dcps Btg2 Lsm6 Dnajc1 Hexim1 Skil Ye s1 Abcb4 Dnajc1 Hexim1 Zyx Arhgap35 Myl12a Ptprj Abcb10 Abcb4 Gamt Cndp2 Pabpc4 Arhgap35 Abcb10 Zyx Luc7l2 Gamt Cndp2 Pabpc4 Ccnc Ptprj Bid Crb3 Bid Luc7l2 Got2 Exosc2 Tob1 Ccnc Myl12b Crb3 Casp7 Gls2 Exosc2 Casp7 Pipox Got2 Tob1 Myl12b Slc25a25 Gls2 Ik Ywhaq Pipox Ik Cnot6l Slc25a25 Gnmt U2af2 Rrbp1 Lmo7 Ywhaq Cnot6 Cnot6l Gnmt U2af2 Rrbp1 Lmo7 Aifm1 Ywhaz Exosc5 Cnot6 Ubqln1 Aifm1 Ywhaz Slc25a42 Srsf5 Rbmxl1 Exosc5 Ubqln1 Ccdc101 Slc25a42 Matr3 Srsf5 Med11 Zfr Nono Rbmxl1 Exosc10 Ccdc101 Dffa Matr3 Med11 Ptpn1 Tjp3 Nono Snrpa1 Diap1 Dffa Hint1 Zfr Exosc10 Dhx36 Cdk8 Diap1 Ptpn1 Tjp3 Hint1 Snrpa1 Ccbl1 Hnmt Dhx36 Cdk8 Sf3a1 Ccbl1 Hnmt Edc3 PPabpc1abpc1 Hsph1 Decr2 Abcc2 Sf3a1 Ilf2 Edc3 Hsph1 Paox Decr2 Srsf2 Exosc9 Med16 Paox Abcc2 Srsf2 Ilf2 Exosc8 Exosc9 Hspa4l Med16 Slc25a23 Exosc8 Skiv2l2 Exosc7 Hspa4l Dock1 Baiap2 Cask Slc25a23 Mocs3 Skiv2l2 Exosc7 Dock1 Baiap2 Cask Casp6 Scly Cth Mocs3 Ssx2ip Casp6 Scly Cth Ctu1 Ssx2ip Ptpn6 Srsf6 Maob Ddx6 Ptpn6 Epb4.1 Srsf6 Maob Ctu1 Cnot2 Ddx6 Sec31a Epb4.1 Ywhab Urm1 Tr mu Cnot2 Wdr61 Sec31a Ywhab Snrpc Urm1 Tr mu Wdr61 Dnajb12 Snrpc Cnot8 Lsm5 Dnaja1 Dnajb12 Nudt19Nudt19 Crot Wasf2 Eftud2Eftud2 Pcbp2Pcbp2 Gpt2 Cnot8 Lsm5 Wasf2 Rad21 Slc25a45 Gpt2 Mat2a Rad21 Slc25a45 Glyat SmSmu1u1 Auh Mat2a Pex13 Mpdz Glyat Rbm14 Elavl1 Auh Cnot7 Lsm3 Pex19 Pex13 Mpdz Rbm14 Elavl1 Cnot7 Lsm3 Skiv2l Pex19 Stag1 Gstt1 Skiv2l Entpd4 Stag1 Gstt1 Entpd4 Pfn1 Srrm2 Pfn1 Srrm2 P4ha2 Pex7 Ywhag Snrpd3 Nfs1 Ap4b1 Gm21685 Pex7 Ywhag Anapc2 Snrpd3 Nfs1 Bbox1 P4ha2 Cnot3 Ap4b1 Gm21685 Stag2 Bbox1 Cnot3 Ap3s1 Ctsf Stag2 Anapc2 Ccbl2 Ap3s1 Ctsf Mgst3 Sdsl Lsm1 Pxmp2 Cdk4 Ccbl2 Mgst3 Sdsl Lsm1 Pxmp2 Cdk4 Lap3 Cnot4 Ywhah Lap3 Srsf7 Cnot4 Lsm4 Pex11a Ywhah Pah Srsf7 Srsf1 Lsm4 Sec22a Cln3 Pex11a Pah Srsf1 Sat2 Sec22a Cln3 Ap3s2 E2f5 Cul1 Ahcy Stxbp6 Ap3s2 Hdac1 E2f5 Bub3 Cul1 Sat2 Hspd1 Stxbp6 Tap2 Hdac1 Bub3 Ahcy Ap3m1 Dyrk1a Hspd1 Tap2 Ttc37 Arsg Ap3m1 Dyrk1a Anapc7 Ttc37 Hspa9 Stxbp5 Arsg Anapc7 E2f4 Sf3b3 Ahcyl1 Stxbp5 Ctsc Hdac2 E2f4 Ahcyl1 Hspa9 Sf3b3 Ctsc Hdac2 Snrpe Lsm2Lsm2 Parn Snrpe Parn Cdc14b Snrpd2 Pex16 Smc3 Cks1b Cdc14b Snrpd2 Sat1 Ap1m1 Pex16 Smc3 Cks1b Sat1 Sds SumfSumf11 Ap1m1 Cdc26 YwhaYwhaee Hnrnpa1 Hnrnpa1 Sds Pex10 Cdc26 Gstt2 Tcerg1 Cln5 Bclaf1 Ddc Cln5 Pex10 Rabggta Gstt2 Bclaf1 Tcerg1 Hgd Rabggta Hgd Ddc Dct Pycrl Dct Gpt Slc25a17 Cks2 Pycrl Thrap3 Abat Gpt Slc25a17 Cks2 Thrap3 Abat Gm2a Ctsa Agxt Nat2 Gm2a Gsta3 Nat2 Mad1l1 Cdk6 Gsta3 Mad1l1 Cdk6 Hnrnpa3 Usp39 Cbx3 Cherp Hnrnpa3 Sf3a3 Usp39 Cbx3 Mcee Npc2 Smc1Smc1aa Cherp Sf3a3 SnSnrnrnp200p200 Mcee ImpaImpa11 Sf3a2 Aldh6a1 Sf3b6 Sf3a2 Aldh6a1 Psap Sf3b6 Ctns Psap Impa2 Ctns Tpp1 Uroc1 Impa2 Tpp1 Uroc1 Got1 Acy1Acy1 Agmat Suox Got1 Ctsh Agmat Suox Serpina1c Nags Ap4s1 Prodh Ctsh Serpina1c Nags Ap4s1 Tdo2 Prodh Phyh Prpf8 Tdo2 Hibch Prpf8 Hibch Prdx1 CrCratat PmvkPmvk Ddx39b Prdx1 Ddx39b Mat1a Prdx5 Abcd1 Abcd1 Mbl2l2 Sf3b2Sf3b2 ND1 Adi1Adi1 Srm Sf3b1 Cd82 ND1 Sf3b5 Sf3b1 Cd82 Lgmn Pex14 PePex2x2 Sf3b5 Lgmn Pex14 Hibadh Aadat Hibadh Aadat Snrnp40 Snrnp40 Prpf6 Shmt2 Ctsz Prpf6 Shmt2 Ctsz Scarb1 Otc Ctsb Cltc Scarb1 Haao Otc Ctsb Cltc Pex3 Haao Pex3 Steap3 Mbl1 Impa1 Steap3 Ap3b1 Mbl1 Impa1 Ap3b1 Mpv17l Pcca Spr Mpv17l Pex11b Pcca Spr Arg1 Ctsl Pex11b Casp8 Arg1 Casp8 Amdhd1 Ctsl Ndufv1 Amdhd1 Serpina1b Ndufv1 PePex11gx11g Nat2 Serpina1b Shmt1 Nat2 Car1 Shmt1 Car1 Apip Pex5 Slc25a5 Apip Pex5 Slc25a5 HaHall Pxmp4 Sqrdl Scarb2 Pxmp4 Itgav Car14 Scarb2 Itgav Mmab Car14 CltbCltb Mmab Cbss Prodh2 GlyctGlyctkk Lmna Ndufb8 Mfsd8 Hacl1 Atp6v0e Flad1 Ndufb8 Prdx6 Clta Mfsd8 Hacl1 Atp6v0e Flad1 Ppa2 Prdx6 Ppa2 Nit2 L3hypdh Ap1b1 Sfn Nit2 L3hypdh Ap1b1 Sfn LampLamp22 Pex1 Ap1g1 Pex1 Laptm4b Ctsd Ap1g1 Ndufa12 Laptm4b Cd63 Ctsd Ndufa12 Cd63 Nnt Chdh Mettl6 Mri1 Nudt7 Nnt Amt Chdh Mettl6 Mri1 Abcd3 Nudt7 Amt Abcd3 Ech1 Cps1 Ndufa5 Laptm4a Cps1 Ndufa5 Ap3d1 Laptm4a Aspa Dnase2a Ap3d1 Sugt1 Cox7a2l Aspa Ehmt1 Dnase2a Hykk Mgst1 Sugt1 Ywhaq Cox7a2l Ehmt1 Hykk Mgst1 Ywhaq Nagpa Gstm1 Ndufc2 Nagpa Gstm1 Ndufc2 Alas2 Fech Alas2 Ehmt2 Fech Prkar2a Car8 Alas1 Ehmt2 ItgbItgb55 Acp2 Prkar2a Car8 SrSrrr Alas1 Lamp1 Agxt2 Gm4952 Acp2 Ndufc1 Lamp1 Slc11a2 Agxt2 Gm4952 Slc11a2 Ndufc1 Dnase2b Ap1s1 Abca2 Adck5 Dnase2b Ap1s1 Abca2 Mut Glud1 Adck5 Ywhaz Dync1h1 Glud1 Ywhaz COX2 Amd1 Mpv17 Dync1h1 COX2 Amd1 Slc17a5 Mpv17 Ppa1 Slc17a5 Ppa1 Rilp Tap1 Plod3 Rilp Tap1 Plod3 Gls2 Gga2 Gga1 Gls2 Gga2 Gga1 Mpv17l2 Car5a Npc1 Sort1 Mpv17l2 Vkorc1 Car5a Inmt Npc1 Sort1 Abcb11 Inmt Abcb11 Vkorc1 Ywhab Atp6v1h Glt25d1 Dync1i2 Dync1li2 C3 Endog Ywhab Ndufs5 Atp6v1h Glt25d1 Whsc1 Dync1i2 Dync1li2 C3 Endog Ndufs5 Whsc1 Cox17 Abcb6 Cox17 TkTk11 Abcb6 TkTk22 Colec12 Abcg8 Uqcrfs1 Colec12 Abcg8 Uqcrfs1 Blvra Uckl1 Kat5 Ggcx Blvra Uckl1 Kat5 Sardh Ggcx Cox7a2 Uck2 Dynll1 Sardh Cox7a2 Uck2 Dynll1 CmpkCmpk11 Atg4b Dpysys UcUck1k1 Atg4b Pnpo YwhahYwhah Hint1 Dut Atg1Atg133 Rdh11 Hint1 Dut Becn1 Abcb7 Rdh11 Glul Slc25a3Slc25a3 Becn1 Atg4d Abcb7 Glul Atg4d Hmbs Gstz1 Atg7 Hmbs Gstz1 Atg7 Miff Ado Atg4a Ado Atg4a Ulk1 Dctpp1 Ulk1 Abca1 Dctpp1 Slc26a1 Slc16a7 Abca1 Hccs Pcbd2 Slc26a1 Slc16a7 Abca66 Hccs Ass1 Pcbd2 Ulk2 Abca8b Cox5a Mtap Slco2b1 Ass1 Ulk2 Abca8b Cox5a ATP6 Mtap Slco2b1 ATP6 Idi1Idi1 GstmGstm77 Phykpl Phykpl Atg3 Dynll2 Naglu Cpox Ndufa13 Uqcrb Car3 Atg3 Dynll2 Naglu Cpox CpCp Adck3 Uqcrb Car3 Adck3 Csad Gsta4 Dbt Csad Gsta4 Atp6v1f Dbt Alg2Alg2 Pccb Ywhag Cox6b1 Atp6v1f Aadat Cps1 Aadat Acmsd Pccb Cox6b1 Adck4 Bub3 Cps1 Acmsd Bub3 Asl Hexa Adck4 Asl Slc22a3 Hexa Slc22a3 DpDpydyd Gstm4 Hexb Gstm4 Ppm1k Slc35dSlc35d11 Hexb Ppm1k Gxylt1 Dpys Klc4 Aga Gxylt1 Cda Dpys Klc4 Aga Gstm2 Mut Agmat Cda Ctps2 Gstm2 Mut Agmat Ctps2 SuSuoxox Slco1a11 AnpeAnpepp Qdpr Chst13 Upp1 Slco1b2 Vdac2 Qdpr Chst13 Upp1 Klc1 Slco1b2 Vdac2 Gstm6 Gstm3 Alg11 Klc1 Gstm6 Gstm3 Alg11 Ext2Ext2 Dpyd Pdxk Dpyd Acad8 Pdxk Carkd Extl3 Acad8 Fah Carkd Extl3 Ftcd Setd2 Fah B4galt3 Upp2 Ftcd Hs2st1 B4galt3 Umps Gnmt Setd2 Alg8 Upp2 Hs2st1 Dtymk Umps Gnmt Alg8 Dtymk Pccb Hibadh Ido2 Gyg Hsd17b10 Pccb Hibadh Ido2 Gyg Chpf2 Chpf Gfpt1 Hsd17b10 Chpf2 Chpf Gfpt1 Ext1Ext1 Alg2 Alg2 Sqrdl Pcbd1 Aifm1 Ywhae Naglu Sqrdl Ywhae Ndufb7 Ndufb9 Naglu Acp6Acp6 Gstt33 Ak3 Rdh16 Ndufb5 Rdh16 Atp13a1Atp13a1 Ndufb5 Slc2a9 Pomgnt1 Pomgnt1 Agxt2 Slc2a9 Cad Pgap1 Agxt2 Cad Pgap1 Fuca1 Clybll Hexb Fuca1 Slc35a3 Hexb Pah Slc35a3 Ppox Rfk Pah Ppox Alad Rfk Tymp Alad Pomt2 Pipox Tymp Pomt2 Pipox Gm4952 Smc1a Cox7c Gm4952 Smc3 Smc1a Cox7c Pomt1 Smc3 Psph Pomt1 Asna1 Psph Asna1 Hexa Ids Btd Tgm1 Casp6 Atp6v0a1 Upb1 Tgm1 Ids Btd Atp6v0a1 Hexa B3gat3 Upb1 Vapb Fahd1 Oplah Casp6 Rpn2 B3gat3 Rpn2 Fahd1 Cad Vapb Oplah Gcnt2 Rpn2 Rpn2 Hmox2 Pigs Gcnt2 Poglut1 Cad Hmox2 Pigs Poglut1 Atp6v0a2 Ogt Atp6v0a2 Atp5a1 Ogt Extl2 St6gal1 Atp5a1 Extl2 St6gal1 Ogdh Asph Aga Grhpr Aass Fdxr Ogdh Txndc12 Asph Aga Grhpr Aass Fdxr Tyms Txndc12 Tcirg1 Pigk Tyms ArArmcmc11 Gldc Aldh1a7Aldh1a7 Tcirg1 Pigk Gldc Gnss Mif UrocUroc11 Dhrs4 Vcl Atp6v1g1 Cox15 Vcl Pfn1 B3gnt1 Cdo1 Txnrd2 Atp6v1g1 Cox15 Pfn1 Galns B3gnt1 Gpaa1 Cdo1 Txnrd2 Gpaa1 St3gal5 Myh10 Galns St3gal5 Myh10 Man2c1 Tspan14 Man2c1 Tspan14 ArsbArsb Txnrd1Txnrd1 Vnn1 Cox11 Rdh14 Cgn Glyat Vnn1 Rdh14 Cox11 Alg5 Gba Pcyox1 Cgn Alg5 Gba Dhodh Glyat Pcyox1 Mccc1 Urod Dhodh Mccc1 Bckdha Bckdhb Urod PigxPigx KyKynunu Bckdha Bckdhb Cbr4 Actn1 HyHyalal22 Txnrd2 Glud1 Actn1 Man2b1 Mgat1 Glce St3gal1 Txnrd2 Mgat1 Glce Tecr Aldh1a1 Man2b1 St3gal1 Sms Tecr Aldh1a1 Uqcrc2 Man2a1 Sms Asah1 Uqcrc2 Man2a1 Ggcx Mgat1 Asah1 Nnt Hykk Ggcx Blvra Nnt Tgds Hykk Mgat1 Gclm Pofut2 Rabggta Blvra Tgds Hlcs Kynu Gclm Pofut2 Tymp Rabggta Hlcs Kynu Tjp2 Tymp Tjp2 HgsnatHgsnat Hsd17b12 Alg3 HyHyalal11 Pycr2 Hsd17b12 Alg3 Pcca Pycr2 C1galt1 Rabggtb Sardh C1galt1 Pcca Lap3 Stt3b Rabggtb Coq3 Lap3 Sardh Hccs Dhdds Mccc2 Gstk1 Coq3 Stt3b Hccs Dhdds Mccc2 Gstk1 GanaGanabb Alg6 Cpox Pank1 Gba Dhcr24 Alg6 Hmbs Cpox Pank1 Fahd1 Fah Gba Dhcr24 Engase Pigh Neu1 Hmbs Nadk Fahd1 Fah Engase Pigh Neu1 Nadk Coq6 Galnt1 Ppcdc Pycrl Coq6 As3mt Pigv Pigt St3gal3 Galnt1 Ppcdc Thtpa Gsr Pycrl Bckdha As3mt Pigv F5 Pigt St3gal3 Thtpa Gsr F5 Atp5b Nudt9 Stt3Stt3aa Bckdha GnGnss Cox8a Atp5b Nudt9 Cox8a Txnrd1 Gcdh Lipt2 Gldc Txnrd1 Gcdh Aplp2 Lipt2 Gldc Hsd17b10 Aplp2 Pigp Galns Mpdu1 Pigp Dpm2 Aasdhppt Hsd17b10 Galns Mpdu1 ArsbArsb Dpm2 Aasdhppt Pank3 Lipt1 Cttn MgatMgat22 Pank3 Acp1 Lipt1 Cttn Mgat4b Acp2 Acp1 Man2b2 Mpdu1 Mgat4b Xylt2 Acp2 Ppcs Alg5 Man2b2 Mgll Mpdu1 Xylt2 Ppcs Nampt Alg5 Lta4hLta4h Mgll Urah Enpp4 Dolk Btd Coq7 Nampt Aass Btd Coq7 Urah Enpp4 Dolk Pnpo Gss Aass Lepre1 Pnpo Gss Lepre1 Bdh1 Ndst2 Man2b1 Bdh1 Mgat5 Ndst2 Man2b1 Eci2 Myh9 Mgat5 Tsku St6gal1 Eci2 Myh9 Mccc1 Tsku Mccc1 Bckdhb St6gal1 Gclc Pigf Bckdhb Gclc Hs6st1 Pigf Ndst1 Hs6st1 Bdh1 Zmpste24 Pigc Ndst1 Bdh1 Zmpste24 Dguok Pigc Pigyll Bdh2 Lias Man2a1Man2a1 Dguok ElElovovl6l6 Bdh2 Lias Actn4 Flad1 Nt5c2 Rdh11 Coasy Flad1 Ndufb2 Nt5c2 Cyp26a1 Asah1 Rdh11 Gpx4 Coasy Ndufb2 Cyp26a1 Asah1 Urod Uros Gpx4 Uros Cyp2a12 Cyp2a5 Sucla2 Pcyox1 Cyp2a5 Sucla2 Nt5c3 Znrd1 Pcyox1 Upb1Upb1 Uqcrh Nt5c3 Nt5c Znrd1 Alad Hmgcl Uqcrh Nudt5 Nt5c Alad Cyp2a4 Hmgcl Nudt5 Rrm2b Cyp2a4 Rrm2b Nmnat1 Spr Nmnat1 Spr Nsdhl Dhodh Nsdhl Dhodh Dhrs3 Mvd Rdh5 Dhrs3 Tjp1 Adk Mvd Nmnat3 Tjp1 Myl12a Nt5m Rdh5 Ntpcr Adk Nmnat3 Myl12a Nt5m Mdh2 Cbr1 Vapa Ntpcr Lpl Mdh2 Cbr1 Vapa Qprt Baiap2 Lpl Xdh Qprt Ptpn1 Baiap2 C8b Xdh NsdhNsdhll Tecr Ptpn1 Polr1e Tecr Gch1 Tap2 Polr1e Gch1 Hpd Tap2 Aprt Hpd Aprt Acox1 Serpina1e Stx12 Acox1 Serpina1e Fech Stx12 Cant1 Twistnb Mbl1 Mbl2 GaGartrt Cant1 Twistnb Gstt1 Fech Acp5 Mbl1 Mbl2 Chka Gstt1 Acp5 Myh14 Chka Dtymk Myh14Tjp3 Nudt2 Sptlc2 Coq2Coq2 Dtymk Tjp3 Nudt2 Sptlc2 Tat Pts Cask Gmps Tat Pts Mocs1 Cask Gda Gmps Mocs1 Gda Sptlc1 Acox3 Acsl1 Ampd2 Sptlc1 Acox3 Acsl1 Ampd2 Ak4 Chkb Oplah Agpat2Agpat2 Ilvbl Ak4 Chkb Oplah NmNmrkrk11 Ilvbl Scarb1 Paics Rrm1 Ganab Urah Scarb1 Esd Paics Rrm1 Ganab Urah Dync1hDync1h11 Esd Mmab Gda Adssl1 Adss Mgll Hsd17b12 Gsto11 Mmab Gda Adssl1 Adss Mgll Hsd17b12 Eprs Lta4h Suclg2 Dync1li1 Nudt16 Lta4h Suclg2 Dync1li1 Nudt16 Blvrb Enpp3 Nt5c Blvrb C3 Atic Enpp3 Kdsr Nt5c C3 Cfh Atic Cfh Kdsr Coq6 Vnn3 Coq6 Zmpste24 Vnn3 Zmpste24 Pde9a Enpp1 Rdh10 Pde9a Enpp1 Dhcr24Dhcr24 Gstp1 Rdh10 Cfb Ak2 Paics Cfb Ppat Ak2 Paics Ppat Soat2 Lipt1 Dguok Soat2 Nnmt Entpd8 Lipt1 Dguok Nnmt Papss2 Entpd8 VnnVnn11 AticAtic Phospho2 Acox1 Papss2 Phospho2 Ephx2 Acox1 Itpa Ephx2 Itpa Cyp4f144 Pecr RetsaRetsatt Naprtt Gart Adk Pecr Mgst3 Gart Pnpt1 Adk Decr2 Mgst3 F8 Rdh16 Manba Ak3 Pnpt1 Decr2 F8 Rdh16 Manba Ak3 Gmpr2 Pnp Gmpr2 Pnp Cryz Acsl5 Crot Impdh2 Cryz Acsl5 Crot Aqp8 Impdh2 Uox Itpa Pxmp2 Uox Itpa C4b Pnp Hmgcs2 Gstt2 C4b Adsl Pnp Hmgcs2 Coq5 Adsl Cyp4f1Cyp4f133 Coq5 Pex19 Pex19 Taz Idh1 Slc47a1 Taz Idh1 Slc47a1 Guk1 Guk1 Guk1 Agpat2 Guk1 Ebp Urad Agpat2 Papss2 Urad Papss2 Gpx1 Crat PePex1x166 Aqp11 Lpin1 Gpx1 Crat Aqp11 Lpin1 Hmgcs1 Elovl1 Slc25a19 Stt3a Hmgcs1 Elovl1 Klkb1 Slc25a19 Stt3a Cfd Klkb1 Acox3 Cfd Slc48a1 Hmgcs1 Acox3 Nudt19 Pex7 Slc48a1 Sqle Hmgcs1 Xdh Nudt19 Pex7 Entpd5 Sqle Xdh Agpat3 Entpd5 Hmgcll Gstm1 Ak44 Agpat3 Eci1 Dirc2 Slc25a22 Aqp4 Snx27 Agpat6 F9 Dirc2 Slc25a22 Aqp4 Snx27 Agpat6 F9 Nudt2 Nme6 Nudt2 Nme6 Oxsm Slc44a3 Pla2g6 Oxsm Acly Pex3 Slc44a3 Pla2g6 Acly Soat2 Pex3 Slc50a1 Slc25a16 Soat2 Mdh1 Stt3b Slc25a16 Akr1c13 Akr1d1 Slc50a1 Mdh1 Stt3b Akr1c13 Akr1d1 Abcb10 Hmgcs2 Entpd6 Abcb10 Slc41a2 Pde8a Hmgcs2 Entpd6 Pde8a Slc41a2 Pex11a Serpinf2 Slc25a26 Aprt Pex11a Adprm B3galt1 Urad Aprt Serpinf2 Slc25a26 B3galt1 Adprm EhhadhEhhadh Urad Pla2g12b Lypla1 HpHprtrt Fdps Pla2g12b Lypla1 PePex1x1 Fdps Cyp4f13 Slc25a20 Cyp4f13 Slc25a20 Fads6 Adsl Masp2 Fads6 Gcdh Adsl Acsl4 Gcdh Dgat1 Acsl4 Eci2 Dgat1 Dhcr7 Fth1 Dhcr7 Hadha Eci2 Fth1 Nme2 Hadha Ak2 Fads2 Cyp2j5 Fads2 Cyp4f14 Cyp4f14 Sc5d Idh2 Sc5d Slc25a1 Idh2 Fmo1 Slc25a1 Cyp2r1 Cyp2r1 Ehhadh Acox2 Agxt Slc40a1 Acox2 Agxt Slc40a1 Prdx1 Cyp2j6 Ephx2 Cyp2j6 Acot13 Fgg Slc25a23 Acadvl Fgg Slc25a23 Acadvl Eci1 Eci1 PPon3on3 Phyh Chpt11 Fads1 DgatDgat11 Gsta3 Adpgk Cyp39a1 Adpgk Slc25a25 Cyp39a1 Dgkd Kng1 Slc25a25 Fhit Dgkd Kng1 Fhit Suclg1 Dgka Slc25a13Slc25a13 Dgka Aco1 Entpd5 BaaBaatt Dgkz Aco1 Entpd5 Tmem86b Dgkz Pon2 Slc9a3rSlc9a3r11 Tmem86b Pon2 Slc25a38 Gck Serping1 Slc25a38 Gck Pmvk Ebp Pmvk Serping1 Slc8b1 Ebp Slc8b1 Pnpla2 Pnpla2 Pfkl Pex26 B4galnt1 Sdha Pfkl Pex26 Ifi30 Etnk1 B4galnt1 Sdha Acyp1 Etnk1 Idh3a Ifi30 Hao1 Idh3a Acyp1 Acsf2 Pon1 Aqp9Aqp9 Hao1 Pon1 Acaa1b Idi1Idi1 Acp6Acp6 Pex6 Fasn Acaa1b FFadsads22 Pex6 Fasn Ggh Nme1Nme1 Pex11g Rfxap Etnk2 AcadAcadll Ggh Pex11g Cyp8b1 Acot8 Rfxap Etnk2 Sqle Cyp8b1 Acot8 Dlat Nme3 Sqle Alpl Fmo5 Dlat Nme3 Slc39a14 Alpl Mgst1 Fmo5 Slc39a14 Ppt1 Mgst1 Idh3g Ppt1 Idh3g TaTapbppbp Cers6 Cbr1 Coq5 Slc39a13 Cers6 Cbr1 Coq5 Slc39a13 GstmGstm33 Acaa1aAcaa1a Slc9a8 Slc9a8 Hmox2 Fga Hmox2 FhitFhit Fga Ripk2 Pgrmc2 Ripk2 Mboat7 Gstm4 Pgrmc2 Rfxank Mboat7 Gstm4 Idh3b Rfxank Idh3b Slc25a15 Elovl1 Gstk1 Anpep Erbb2ip Slc25a15 Elovl1 Gstk1 Anpep Hadha Erbb2ip Slc7a2 Bco1 Hadha Slc7a2 Gstm5 Alb Bco1 Gstm5 Alb Hacl1 Hacl1 Slc39a11 Ptdss1 Acadl Slc25a39 Slc39a11 Cers2 Tr ip6 Slc25a39 Ptdss1 Cers2 Acadl C8g Kng2 Tr ip6 Prdx5 Kng2 Sgpl1 Dhcr7 Sdhc Hspa4 Sgpl1 Dhcr7 Sdhc Prdx3 Hspa4 Oas1g Prdx3 Oas1g Acadvl Acadvl Gclm Gstm6 Acss2Acss2 Acaa1b Enpp2 Acaa1a Gstm6 Acaa1b Enpp2 Acaa1a Tm7sf2 Abcd1 Pcyt1a Tm7sf2 Abcd1 Slc25a11 Pcyt1a Aco2 Pck1 Slc25a11 Uox Aco2 Pck1 Uox Raet1e Raet1e Lcat Pros1 Lcat Pros1 Gpd2 Adh5 AgAgkk Gpd2 Adh5 Cd81 Acadsb Gsta1 Prdx4 Acadsb Gsta1 Cyp4a12b Prdx4 Pex14 Pld3 Pecr Dlst Aldh9a1 Cyp4a12b Pex14 Pld3 Pecr Agpat3Agpat3 Dlst Aldh9a1 Nos1ap Naga Ctsc Nos1ap Naga Elovl2 Abcd3 Slc6a13 Elovl2 Ctsc Abcd3 Fgb Slc10a2 Slc6a13 Gsta2 Fgb Slc2a8 Slc25a42 Slc10a2 Nadsyn1 F10 Slc25a42 Gsta2 Nadsyn1 F10 Slc2a8 Lypla2 Slc6a12 Slc39a9 Lypla2 Txndc12 Slc6a12 Slc39a9 Txndc12 Gstp2 Pex11b Fkbp5 Slc25a33 Slc25a33 Gstp2 Pex11b Fkbp5 Pxmp4 Pgrmrmc1c1 Gm2a Pxmp4 Slc38a10 Sc5d Gm2a Slc38a10 Sc5d Gclc Pgp Msmo1 Gclc Pgp Cyp4a14 Msmo1 PePex5x5 St3gal4 Fasn Cyp4a14 St3gal4 Fasn Lypla1 AbcbAbcb44 Lypla1 Fam213b Fam213b Slc6a6 Slc23a1 Slc39a1 Acer3 Pcyt2 Slc6a6 Slc23a1 Slc39a1 Acer3 Pcyt2 Angptl4 Aldoa Rab3d Aldoa Rab3d Slc39a3 Ppap2c Angptl4 Pgam1 Slc39a3 Ppap2c Ppap2b Pgam1 Fkbp4 Slc6a9 Ppap2b Fkbp4 Abcb8 Slc6a9 Gpcpd1 Abcb8 Gpcpd1 Nqo1 Slc22a14 Scd1 Nqo1 Npc2 Cfi Slc25a47 Slc22a14 Scd1 Tspan4 PrdxPrdx22 Npc2 Tspan4 Slc25a44 Icmt Slc25a44 Icmt Cs Gstm2 Cs Ctsf Abcc6 Gstm2 Ctsf Cr1l Abcc6 Pla2g16 Gsta44 Tcn2 Cr1l Pla2g16 Tcn2 Ankrd3Ankrd366 Fads1 Oxsm Cyp4a12a Por Lmbrd1 Tm7sf2 Fads1 Oxsm Cyp4a12a Por Lmbrd1 Ctsb C4bp Sgms2 Degs1 Tm7sf2 Ctsb B2m C4bp Abcc3 Sgms2 Degs1 B2m Abcc3 Acot13 Pgs1 Elovl2 GstmGstm77 Pgs1 Elovl2 Cyp39a1 Ech1 Elovl3 Cyp39a1 Ech1 Elovl3 Rfk Slc25a45 Acaa2 Rfk Slc25a45 Acaa2 Slc46a1Slc46a1 Aldh1a1 Tm9sf2Tm9sf2 Ptges3 Ept1 Crls1 Aldh1a1 Ctsh Cd36 Ptges3 Ept1 Nudt12 Ctsh Cd36 Crls1 FaFam213bm213b Nudt12 Ap1m1Ap1m1 Pla2g15 Hoga1 AI482555 Pla2g15 Hoga1 AI482555 Msmo1 Cyp4a31 DhrsDhrs44 Cyp2j9 Apoa4 Nfyc Msmo1 Cyp4a31 Apoa4 Nfyc Cyp2j9 Slc38a4 Cyp2u1Cyp2u1 Ptdss2 Slc38a4 Ptdss2 Hagh Ifih1 Hagh Dhx58 Isg15 Ifih1 Dhx58 Isg15 Slc22a28 Sgpp1 Slc46a3 Nlrx1 Slc22a28 Sgpp1 Sdhb Tm9sf4 Nudt7 Slc46a3 Nlrx1 Sdhb Mavs Ugcg Tm9sf4 Nudt7 Mavs Nfyb Azi2 Ugcg AcadmAcadm Ptges2 Tank Azi2 Ptges2 Nfyb Sike1 Sike1 Tank Slc19a2 Gnpat Sphk2 Pla2g12b Lipc Gnpat Sphk2 Pla2g12b Slc19a2 AbcbAbcb66 Slc25a5 Lipc Ldha Cyp2j55 Slc27a5 Slc25a5 Cyp4a10 Ldha Slc27a5 Pnpla7 Cyp4a10 Slc27a4 Pla2g12a Ctsa Slc27a4 Arsa Pla2g12a Acadsb Ctsa Arsa Psap Slc22a30 Acadsb Psap Slc22a30 Slc22a15 Qdpr Slc22a15 Qdpr Elovl5 Cds2 Slc33a1 Hsd17b7 Elovl5 Cept1 Cds2 Agk Slc33a1 Hsd17b7 Cept1 Agk Aldh1a7 Reep6 Etfa Aldh1a7 Reep6 Etfa Abcc2 Acot3 Tpp1 Napsa Abcc2 Acot3 Mecr Tpp1 CtslCtsl Napsa Slc22a7 Acot4 Mecr Slc22a7 Acot4 Lcat Igf2r Atg7 Igf2r Atg7 Rcan1 Slc22a23 Lcat Ppt2 Rcan1 Slc22a23 Abca6 Etnppl Gpx1 Ppt2 Slc26a1 Abca6 Etnppl Gpx1 Slc26a1 Slc38aSlc38a22 HadhHadhbb Dld Hadhb Apoa5 Acot1 Hadhb Mpv17 Apoa5 Acot1 Mpv17 Slc3a1 Lipa Ggct Slc3a1 Slc35f5 Lipa Echs1 Ggct Lamp1 MttpMttp Slc35f5 Echs1 Acat2 Sdhd Akr1a1 Ppt1 Acadm Lamp1 Acat2 Cyp4a12a Ppt1 Acadm Cyp4a12a Slc4a7 Pdxk Pdk2 Slc22a18Slc22a18 Slc4a7 Gpd1 Pdxk Cyp8b1 Pdk2 Reep5 Cyp8b1 Slc35d1 Cyp4a12Cyp4a12bb Reep5 SgplSgpl11 Apob Abcg8 Abcg5 Slc35d1 Tpmt LgmnLgmn Dynll2 Abcg8 Slc35e2 Cyp4f15 Plin2 Tpmt Cp Ctss Apob Abcg5 Dynll2 Vdac2 Slc35e2 Cyp4f15 Plin2 Cp Ctss Stxbp2 Vdac2 Slc35d2 Acat1 Stxbp2 Slc35d2 Pdss2 Acat1 Slc3a2Slc3a2 Slc16a2Slc16a2 Pdss2 Acp5 Ap1b1 Slc2a9 Mocs1 Slc2a9 Slc4a2 Mocs1 Lamp2 Cltc Slco1b2 Slc4a2 Lamp2 Cltc Klc4 Slco1b2 Slc35c2 Acaca Dhrs7b Ctsd Klc4 Slc35c2 Acaca Cyp27a1 Dhrs7b Ctsd PisdPisd Ptplbb Ap1g1Ap1g1 Slc16a10 Dpp4 Slc16a10 Abca8a Cers2 Dpp4 Nceh1 Abca8a Cers2 Nceh1 Abca1 LsLsss Cyp4a14 AdssAdss Mecr Abca1 Slco2b1 Slc35c1 Cyp4a14 Mecr Acaa2 Slco2b1 Slc35c1 Acaa2 Cstb Cyb561 Slc35b2 Cstb G6pc Enpp3 Adssl1 Mboat7 Cyb561 Slc17a1 Slc35b2 G6pc Enpp3 Adssl1 Mboat7 Slc17a1 Smpd1 Gpd2 Slc17a4 Hadh FntaFnta Smpd1 Dhrs3 EnppEnpp11 Ctsz Slc17a4 Hadh Dhrs3 Pfas Mdh2 Mvk Cnp Pfas Mdh2 Mvk Cnp Csk Retsat Mocs2 Pkdcc Capza2 Csk Retsat Pkdcc Capza2 Scarb2 Pcbd2 Abcb7 Slco2a1 Mocs2 Camkk2 Scarb2 Abcb7 Slco2a1 Camkk2 Amacr Pcbd2 Amacr Ap3b1 Pafah1b3 Pemt Cap1 Gmps Cltb Ap3b1 Slc35b4 Pafah1b3 Pemt Cap1 Gmps Cltb Slc17a3 Slc35b4 Pafah1b1 Rdh10 Capza1 Slc17a3 Pafah1b1 Rdh10 Tbck Capza1 Pcyt1a Clta Nnmt Tbck Dhdh Pcyt1a PtgesPtges33 Clta Slc16a5 Slc35b1 Eprs Dhdh Slc35b1 Pafah1b2 Pgk1 Gpam Col18a1 Slc16a5 Eprs Pafah1b2 Pgk1 Aldob Col18a1 Ogdh Aldob Pcyt2 Gpam Dak Dgat2 Pcyt2 Slco1a4 Ogdh Smpd2 Dak Dgat2 Pld3 Slco1a4 Acads Adck2 Acads Npc1 Ap3d1 Slc10a1 Slc17a2 Smpd2 Pld3 Acads Adck2 Lypla2 Acads Npc1 Ap3d1 Slc10a1 Slc17a2 Csk Pcbd1 Lypla2 Csk Pcbd1 Slc16a11 Slc16a11 Slco1a1 Tm9sf3Tm9sf3 Slco1a1 Adck1 Adck5 Cds2 Nrbp1 Adck1 Adck5 Cds2 Nrbp1 Anxa4 Irf3 Tex14 Anxa4 Irf3 Acly Gpam Tex14 Mrs2 Mrs2 Acly Gpam Nudt3 Abca3 Slc33a1 Nudt3 Abca3 Tollip Aldh7a1 Slc33a1 Slc16a7 Slco1a5 Pafah2 Tollip Aldh7a1 Hsd17b7 Slc16a7 Slco1a5 Pafah2 Adck4 Hsd17b7 Fdft1 Pck1 Parg Nrbp2 Adck4 Fdft1 Slc13a3 Nrbp2 A2m Pck1 Parg Slc13a3 Slc20a1 Mdh1 Krt8 Mvp Mvp A2m Slc20a1 Mdh1 Mvp Slc35a1 Ptges2 Krt8 Mvp Slc35a1 Naprt Fpgs Ublcp1 Slc15a4 Ptges2 Naprt Ublcp1 Fpgs Nuak2 Lipa Slc15a4 Nuak2 Stom Apoh Lipa Slc35a4 Stom Apoh Pigr Cpt2 Pigr Slc20a2 Sdha Rab3gap1 Pafah2 Slc22a1 Slc35a4 Cpt2 Nudt4 Slc22a1 Slc20a2 Slc35a2 Sdha Nudt4 Rab3gap1 Pafah2 Lpgat1 Slc35a2 Cyp5Cyp511 Adprhl2 Pdf Capzb Lpgat1 Lss Hsd3b7 Slc30a10 Tatdn3 Adprhl2 Capzb Hsd3b7 Cnnm2 Fmo1 Pdf Lss Blvrb Tatdn3 Cnnm2 Slc30a10 Blvrb Fmo1 AdAdckck33 Actr3 Tatdn1 Pdp2 Actr3 Stat1 Slc25a3 Asna1 Gch1 Tatdn1 Pdp2 Stat1 Slc25a3 Vapb Fdft1 Lyn Lclat1 Asna1 Vapb Slc17a9 Naga Fdft1 Gch1 Lyn Lclat1 Dpm1 Armc1 Slc17a9 Slc30a9 Naga Pxk Ept1 Dpm1 Atp7b Mettl16 Snrk Ept1 Gpd1 Armc1 Slc30a9 Pxk Atp7b Cpt1a Mettl16 Snrk Pim2 Gpd1 Lpcat3 Atp13a3 Cpt1a Pim2 Atp13a3 Cib1 Lpcat3 Cstb Cib1 StatStat33 Cept1 Acot1 Cstb Slc16a12 Tesk2 Ppm1l Cept1 Acot1 Cyb561d2 Slc16a12 Tesk2 Ppm1l Scyl3 Etfdh Slc30a7 Lpgat1 Tesk1 Scyl3 Cyb561d2 Ntmt1 Ctdnep1 Etfdh Slc30a7 Lpgat1 Tesk1 Nudt14 Fh1 Ntmt1 Ctdnep1 Fh1 Nudt14 Selenbp1 Cbr4 Selenbp1 Sucla2 Agps Cbr4 Slc30a5 Sucla2 Agps Gyk Slc30a5 Gyk Qprt Hif1an Gyk Hif1an Krt18 Gyk Qprt Ppm1k Alpk1 Krt18 Acyp1 Idh2 Galk2 Ppm1k Scyl2 Serpinc1 Slc30a6 Pim3 Alpk1 Acyp1 Idh2 Lclat1 Galk2 Scyl2 Serpinc1 Copg1 Slc30a6 Pim3 Lclat1 Carkd Cope Acot4 Copg1 Mtrr Carkd Atp13a1 Acot4 Cs Mtrr Pskh1 Ppm1m Tr ib1 Atp13a1 Mt2 Aco1Aco1 Aco2Aco2 Cs Lpcat3 Pskh1 Tr ib1 Ppm1m Adh1 Aldoc Lpcat3 Stk38 Pdpk1 C6 Adh1 Slc37a4 Aldoc Stk38 Stk38l Pdpk1 C6 Hsd17b4 Abcb11 Mvk Slc37a4 Fdxr Asph Stk38l Hsd17b4 Tm9sf4 Abcb11 Acot2 Mvk Suclg2 Fdxr Asph Acot2 Tm9sf4 Suclg2 Hyi Tr io Anxa5 Hyi Tr io Akr1e1 Anxa5 Idh1Idh1 Akr1e1 Spast Itm2Itm2cc Fn3k Ppm1g Dusp22 Spast Tm9sf2Tm9sf2 Aldoa Pgp Alkbh1Alkbh1 Ilvbl Fn3k Ppm1g Dusp23 Dusp22 Copg1 Hipk1 Ilvbl Fmo5 Dusp23 Copg1 Aldoa Pgp Hipk1 Fmo5 Clybl Clybl Serpina1d Hipk2 Dusp19 Serpina1d Hipk2 Actr2 Dusp19 Manea Ppm1f Selenbp2 Mgea5 Acsl1 Ppm1f Actr2 Cmbl Ppip5k2 Manea Selenbp2 Mgea5 Acsl1 Cpt1a Cmbl Ppip5k2 Trak2 Cpt1a Trak2 Cyp27a1 Tgm1 Rdh14 Dusp28 Reep5 Ip6k2 Cyp27a1 Tgm1 Rdh14 Dusp28 Reep5 Hipk3 Dusp11 Pglyrp3 Echs1 Cope Ip6k2 Pglyrp3 Cope Reep6 Hipk3 Mmaa Dusp11 Echs1 Mmaa Acsl5 Anxa6 Reep6 Ip6k1 Acsl5 Anxa6 Pcx Ip6k1 Pcx Qpct N4bp2 Gpd1l Gpi1 Qpct N4bp2 Gpd1l Tm9sf3 Gpi1 Hao1 Suclg1 As3mAs3mtt Tm9sf3 Mdp1 Suclg1 Pafah1b1 Dlat Vrk3 Mdp1 Cdk18 Alb Dlat Vrk3 Cdk18 Pafah1b1 Alb Hoga1 Idh3a Ftl1 C9 Fbp1 Hoga1 Idh3a Ftl1 C9 Fbp1 Actr2 Sdhb AcAcoxox22 Serpina1c Actr2 Idh3g Vrk2 Serpina1c Idh3g Vrk2 Vrk1 Vrk1 Acsl4 CrCryzyz Pglyrprp22 Eya3 Acsl4 Saa4 Pgrmc1 Eya3 Acsl3 Cyp7a1 Capza1 Pgrmc1 Apoa2 Saa4 Serpina1b Acsl3 Cyp7a1 Apoa2 Serpina1b Capza1 Mgam Kng1 Capza2Capza2 1300017J02Rik Mgam Kng1 Xylb Pygl Mt1 1300017J02Rik Xylb Pygl Mt1 Mocos Mocos Mfge8 Inpp5b Mfge8 Idh3b Inpp5b Baat Sdhc Idh3b Serpina1e Sdhc Alkbh4 Akr1c13 Cdk12 Serpina1e Cdk12 Man1Man1aa Alkbh4 Prdx4 Akr1c13 Stk25 Prdx4 Pcmt1 Amy1 Stk25 Cat Pcmt1 Amy1 Mmaa Cat Ilkap Mmaa Prdx3 Ilkap Cdk13 Ugt1a6bUgt1a6b Dhdh Ptpn12 Prdx3 Cdk13 Dhdh Ptpn12 Dpm3 Ugdh Pklr Dpm3 Adpgk Ugdh C8b Pklr Mocos Adpgk Ick C8a C8b Cfh Isyna1 Man1a2 Akr1d1 Ick C8a Cfh Mocos Sdhd Isyna1 Man1a2 Pikfyve Akr1d1 Sdhd Pikfyve Oxsr1 Bphl Impad1 C4b Stxbp2 Ptpn2 Oxsr1 Bphl Impad1 C4b Actr3 Stxbp2 Pigq Ganc Ptpn2 Actr3 Pigq ItpkItpk11 Ganc Dohh Acy3 Dohh F10 Acy3 F10 Galm Elovl5 Adh5 Dlst Galm Elovl5 Acacb Adh5 Dlst Acacb Pgrmc2 Xylb Pgrmc2 Rbp4 Xylb Dpagt1 Cryl1 Cr1lCr1l Rbp4 HephHeph Dpagt1 Cryl1 TpstTpst11 Pfkm Pmm2 Serping1 Gck Pfkm Pmm2 Prdx22 Serping1 Fgg Acat1 Anxa4 Krt15 Gck Slc27a5 Fgg Krt15 Cdk16 Acat1 Anxa4 Pfkl Slc27a5 C8g Pfkl Tpst2 Cdk16 C8g AcacAcacaa Apoh Tpst2 Fga Tpi1 Apoh Dolpp1 Lgals3bp Gapdh Atox1 Dolpp1 Amacr Cryl1 Lgals3bp Gapdh Atox1 Bpgm Amacr Fgb Cfi Cryl1 Bpgm Cfi Aldob Amy1y1 Pygl PlcbPlcb11 Fgb Aldob Glb1 Peak1 Ugdh Glb1 Peak1 MsMsnn Ugdh Pi4k2a Ptpn3 Por Pi4k2a Ptpn3 Por Tapbp Tapbp Acot12 Galt Slc39a4 Fabp1 Acot12 Galt Pmm2 Slc39a4 Fabp1 Pmm2 Pklr Ifih1 Plxnb2 Pklr Aldh9aAldh9a11 Ifih1 Plxnb2 Mtmr14 Cd81 Gaaa Mtmr14 Cd81 St6galnac6 Pfkfb1 Pigu Pdha1 Pigu St6galnac6 Pfkfb1 Pik3c3 Pdha1 Gla Frk Gla Pik3c3 Dpm1 Frk Hspa4Hspa4 B2m Slc30a1 Mpi B2m Glb1 Slc30a1 Hadh Dpm3 Mpi Glb1 Hadh Clcn2 Slc31a1 Dpm3 Adhfe1 Pon2 Pon3 Clcn2 Slc31a1 Alg9 Scp2 Adhfe1 Pon2 Pon3 FkbpFkbp44 Pfkfb1 Ddt Alg9 Scp2 Pfkfb1 Gaa Ddt Tsta3 Tpmt Gaa Dad1 Tsta3 Tr it1 Tpmt Fkbp5 Dad1 Tr it1 Fkbp5 Apoa5 Dcxr Ddt Apoa5 Pgm3 Dcxr Anxa5 Ddt Mavs Pgm3 Acy3 Anxa5 Mavs Acy3 Alkbh5 Ugt2b34 Pigl Alkbh5 Ugt2b34 Pigl Inpp1 Amdhd2Amdhd2 Acot8 Inpp1 Gale Gusb Alkbh7Alkbh7 Acot8 Tnk2 Gale Ipmk Gusb Etfdh Tnk2 Ipmk Etfdh Gpld1 Tsta3 Galm Gpld1 Tsta3 Galm Irgm1 Ikbke Irgm1 Ikbke NlrxNlrx11 Ugt1a1 Gusb Ugt1a1 Gusb Cat Dcxr Hsd17bHsd17b44 Mogs Dhrs13 Ldha Dhrs13 Ldha Plin2 Plin2 Dld Mogs Adh4 Irgm1 Dld Mogs Zcchc11 Mtmr6 Adh4 Irgm1 Atl2 Mtmr6 Atl2 Ptpra Zcchc11 Isg15 Krt8 Atl3 Ptpra Isg15 Galk1 Pigg Krt8 Atl3 Atl3 Ntan1 Galk1 Pigg Ntan1 Rbp4 Aldh1b1 Acat2 Atl3 Acat2 Rbp4 Flot1 Aldh1b1 Cst3 Pi4ka Ugt1a10 Zcchc6 Fert2 Cap1 Cst3 Flot1 Pi4ka Ugt1a10 Zcchc6 Qsox1 Msra Fert2 Itm2b AdhfAdhfe1e1 Cap1 Gak Pon1 Selenbp2 Gak Polg2 Pon1 Selenbp2 Stk35 Polg2 Stk35 Camk1 Ugt2b34 Camk1 FlotFlot22 Ugt2b34 FuomFuom Sugct Atl2 Pgm2 Nudt8Nudt8 Sugct Nudt8 Atl2 Pgm2 Nudt8 Zc3hav1 Sbk1 Camk1d Zc3hav1 Naa15 Sbk1 Alkbh6 Camk1d Naa15 Alkbh6 Sorbs1 Naa1Naa155 Sorbs1 Msra Bco2 Dad1 Msra Atp8b1 Bco2 Atp8b1 Ptpn9 Naa16 Ddhd1 Dad1 Lipe Ptpn9 Naa16 Etfa Ddhd1 Lipe Etfa Khk Atp9b Khk Naa30 Cmbl Atp9b Naa30 Cmbl Ptp4a1 Selenbp1 Ptp4a1 Aak1 Selenbp1 Ppp1r3c Aak1 Eno1 Galk1 Nmt2 Ppp1r3c Ugt2b38 Htatip2 Eno1 Galk1 Nmt2 Ugt2b38 Dhrs7b Htatip2 Kif13b Slc12a2 Pam Dhrs7b Loxl3 Kif13b Slc12a2 Atp11c Pam Loxl3 Krt18 Atp11c Atp9a Ptp4a2 Krt18 Sh2b3 Akr1a1 Atp9a Ptp4a2 Sh2b3 Kidins220 Akr1a1 Kidins220 Ppp1r3b Ugt2a3 Sh2b1 Aldh7a1 Ppp1r3b Ugt2a3 Ugt2b5 Sh2b1 Aldh7a1 Ugt2a3 Sugct Ugt2b35 Ugt2b5 Apoa1bp Ugt2a3 Sugct Ugt2b35 Apoa1bp Cyp7a1 Atp11a Cyp7a1 Frs2 Atp11b Srxn1 Copb1 Atp11b Atp11a Mtmr2 Copb1 Atp11c Frs2 Srxn1 Hagh Mtmr2 Atp11c Htatip2 Arhgdia Hagh Uhmk1 Pafah1b2 Dstn Coro1b Htatip2 Uhmk1 Pafah1b2 Dstn Coro1b Arhgdia Haghl Stk1Stk166 Haghl Krt72 Maged1 Krt72 Maged1 Ugt2b37 Fabp2 Fabp1 Decr1 Fabp2 Ugt2b37 Alg1 Fabp1 Alg1 Decr1 Etnppl Scp2 Exoc7 Etnppl Scp2 Exoc7 Coro1c App Pdk2 Coro1c App Ctbs Pdk2 Ugt2b36 Ctbs Apoa2 Ugt2b36 Apoa2 Apoc3 Cpt2 Gdi1 Krt76 Apoc3 Cpt2 Gdi1 Gpld1 Adprh Pdcd10 Krt76 Rft1 Gpld1 Adprh Pdcd10 Homer2 Rft1 Tlk1 Homer2 Acss2 Tlk1 Ubr4 Tlk2 Sod2 Acss2 Ubr4 Pi4kb Tlk2 Sod2 Pi4kb Sod1 Agmo Flnb Ptgr1 Sod1 Agmo Flnb Ptgr1 Fuom Tmod3 Ugt2b1Ugt2b1 Pi4ka Fuom Tmod3 Fbp1 Pi4ka Fbp1 Cd36 Cyp4f15 Flot1 Wnk1 Cd36 Cyp4f15 Flot1 Ugt2b36 Pip5k1a Wnk1 Zc3hav1 Fabp5 Ugt2b36 Pip5k1a Zc3hav1 Saa2 Fabp5 Riok3 Saa2 Tiparp Riok3 Ptgr2 Tiparp Ptgr2 Pip5k1b Gapdh Pip5k1b Anxa6 Parp9 Anxa6 Parp9 Ugt2b1 Ugt2b1 Sord Lmnb1 Lmnb1 Flot2 Sord Flot2 Pgm3 Dhrs1 Apoa1bpApoa1bp Pgm3 Ces1d Dhrs1 Bphl Gdi2 Rpn1 Dhps Nln Anxa11 Ddah1 Dhps Nln Anxa11 Ddah1 Inpp1 Inpp1 Stk40 Gale Stk40 Gale Dio1 Dhrs7 Cdc42bpb Ddah1 Ugt2b35 Ilk Dio1 Dhrs7 Cdc42bpb Ddah1 Ugt2b35 Ilk Msrb11 Pemt Decr1 Plcg1 Pemt Decr1 Plcg1 Slc16a1 Tsg101 Pdik1l Slc16a1 Eea1Tsg101 Pdik1l Lmnb2 Eea1 Lmnb2 Eps8l2 Aatk Rpn1 Eps8l2 Tusc3 Saa1 Git2 Aldh2 Aatk Rpn1 Tusc3 Saa1 Git2 Aldh2 KalKalrnrn AnxaAnxa77 Sept7 Nqo2 Iqsec1 Slc16a1 Sept7 Parp10 Lcp1 Nqo2 Iqsec1 Slc16a1 Parp10 Sh3gl1 Lcp1 Pik3ca Sh3gl1 Hgs Ippk Pik3ca Tmem55b Copb1 Hgs Ippk Tmem55b Copb1 Parp14 Echdc1 Parp14 Msrb2 Iqsec2 Msrb2 Arap1 Iqsec2 Echdc1 Ap2s1 Slc38a3 G6pc ItfgItfg11 Arap1 Capzb Ap2s1 Slc38a3 Vps4b G6pc Iyd Tec Gdi2 Ces1c Capzb Fabp2 Iyd Tec Gdi2 ErErp44p44 Ces1c Vps4b Fabp2 Enpp5 Ces1c Enpp5 Itfg3 Enpep Ces1c Itfg3 Enpep Eps8l2 Usp8 Myo6 Sdcbp Eps8l2 Usp8 Sh3glb1 Prps1l1 Myo6 Erp44 Khk Sdcbp Anxa7 Sh3glb1 Khk Anxa7 Prps1l1 Erp44 Ap2m1 Ap2m1 BcheBche Gdi1 Eea1 Gbe1 Gdi1 Eea1 Arpc1a Actg1 Orm1 Gbe1 Arpc1a Actg1 Orm1 Acot7 G6pc3 Gulo Lcp1 Acot7 G6pc3 Gulo Lcp1 CopbCopb22 Orm1 H2-QH2-Q77 Sh3glb2 Orm1 Sh3glb2 Pdcd6ip Pdcd6ip Tspan33 Car2 Grk6 Mme Tbca Siae Tspan33 Car2 Grk6 Ces1d Tbca Mme Slc27a2 Siae Pgd Ces1d Slc27a2 Ap2a1 Ces3b Igfals Pgd Ap2a1 Myo6 Dbi Ces3b Igfals Aldh3a2 Myo6 Dbi Aldh3a2 Pgls Dhfr Vps25 Map7 Dhfr Vps25 Apoc3 Map7 Tsg101 Smap1 Pgls Apoc3 Ttf1 Cobl Tsg101 Smap1 Ttf1 Parp16 Cobl Parp16 S100a10 Stom Tbcb S100a10 ArArpc1bpc1b Stom Cand1Cand1 Tbcb Ces2a Smap2 Slc1a2 Gphn Ces2a Kif13b Smap2 Rdh13 Ldlr Arfgap2 Slc1a2 Gphn Stk19 Kif13b Rdh13 Ldlr Arfgap2 Minpp1 Stk19 Hook1 Minpp1 Pten Hook1 Psd3 Nmt1 Pten Tbcb Psd3 Msrb2 Nmt1 Ap2a2 Cyb5r3 Ptgr2 Msrb2 Tpi1 Ces1e Tbcb Gna13 Cyb5r3 Ptgr2 Msrb1 Ap2a2 Tpi1 Ces1e Coro7 Agap3 Gna13 Gulo Msrb1 Ces3a Coro7 Uxs1 Agap3 Gulo Ces3a Agt Uxs1 Agt Agl Dnm2 Agap1 Agl Parp9 Dnm2 Map4 Daglb Map4 Cand1 Agap1 Parp9 Sod2 Arpc3 Daglb Dstn Cand1 Rabep1 Sod2 Arpc3 Dstn Ephx1 Rabep1 Ephx1 Vta1 Pdhb Pls1 Vta1 Pdhb Kif21a AcotAcot77 Pls1 Asgr1 Ap2b11 Rtca Parp6 Mtmr4 Kif21a Tbca Napa Rtca Parp6 Mtmr4 Tbca Napa Cyp4vCyp4v33 Ces2Ces2gg IyIydd Faah ChmpLdlr5 ap1 Faah Maea Flnb ChmpLdlr5 ap1 Mtmr3 Maea Cyb5r3 Mtmr3 Ces2e Flnb Aldh1l1 Ces2e Ttll1 Aldh1l1 Svil Abhd6 Ttll1 Add2 Svil Neb Apob Kif5b Abhd6 Syt1 Add2 Tubb5 Neb Apob Cald1 H2- Kif5b Syt1 Acot12 Adh1 Tubb5 Tubb2a Cald1 H2- Arhgef12 Acot12 Adh1 Tubb2a Arhgef12 Pgk1 Add1 Dnm2 Kif3a Dnm2 Ces3b Pgk1 Add1 Ces3a Kif3a Ces3b Epn1 H2- Ces3a Shroom3 Kif16b H2-Q1 Epn1 H2- Kif16b Shroom3 H2-Q1 Myl6 Tu bb6 Tuba1c D1 K1 Tubb6 Slc4a4 Tuba1c D1 K1 Slc4a4 Ces2c Brk1 Shroom1 Adh4 Ces2c Brk1 Shroom1 Coro1b H2-Q8 Apoa1 Dynlrb1 Adh4 Coro1b H2-Q8 Chmp2b Apoa1 Dynlrb1 TuTubb2bbb2b Chmp2b Gbe1 TtTtnn Pdha1 Kif1c Gbe1 Sord Kif1c Crem Pdha1 Sord Tuba4a Crem Gmppb GmppaGmppa Tuba4a Gmppb Aspg Tubb4b Kif1Kif1bb Atp1b3 Iqgap2 H2-Q10 Dbi Aspg Tubb4b Atp1b3 Iqgap2 Myo18a H2-Q10 Dbi Myo18a Slc2a2 Slc2a2 Chmp4b Asap1 Chmp4b Aldh1b1 MyMyo18ao18a Asap1 Aldh1b1 Akr7a5 Prcp Pik3c2a Akr7a5 Kifc3 PpPpl l Prcp Atp1b1 Eml2 Pik3c2a Kifc3 H2- Atp1b1 Pdhx Eml2 Ugp2 Agl H2- Pdhx Ehd1 Eps15 Ugp2 Ehd1 Gbf1Eps15 Agl Nom1 Ssh2 PlecPlec Gbf1 PdhbPdhb Nom1 Ssh2 Gys2 Tpgs2 Rufy1 Chmp3 Pdcd6ip Gys2 Gpatch2 Tpgs2 Rufy1 Chmp3 Pdcd6ip Actb Gpatch2 Actb Stam Ces2a Stam Spata2l Ces2a Gys2 Tns3 Spata2l Gmppb Gys2 Tns3 Gmppb Sptbn4 Katna1 Arhgdia Aacs Sptbn4 Tpm2 Asgr1 Katna1 Arhgdia Aacs Tpm2 Apoa1 Asgr1 Strn Pcif1 Arpc1b Ugp2 Apoa1 Pdhx Tns1 Strn4 Gna13 Strn Pcif1 Arpc1b Ugp2 Tuba1b Pdhx Tns1 Strn4 Gna13 Aldh2 Tuba4a Cmah Agmo Tuba1b Slc4a4 Aldh2 Tuba4a Chmp7 Rgn Cmah Agmo Slc4a4 Eno1 Aldh3a2Aldh3a2 Hgs Chmp7 Rgn Cmah Ap2b1 Hgs Ppp1r12c Eno1 Cmah H2- Ap2b1 Ap2s1 Ppp1r12c Strn3 H2- H2-Q10 Alg14 Strn3 Ap2m1 Ap2s1 H2-Q10 Glo1 Alg14 Mttp Abhd6 Sytl1 Ap2m1 K1 Slc38a3 L2hgdh Glo1 Mttp Abhd6 Sytl1 Arpc1a K1 Slc38a3 L2hgdh Atp1b3 Arpc1a Arpc3 Tuba1c Atp1b3 Mthfs B4galt1 Ppp1r16a Arpc3 Tuba1c Cdc42bpb Mthfs B4galt1 Ddost Phactr4 Ppp1r16a Vps36 Cdc42bpb Ddost Chp1 Phactr4 Vps36 Acsm5 Agt Chp1 Arfgap3 Chmp6 Slc25a10 Acsm5 Agt Arfgap3 T23 Chmp6 Slc25a10 Acsm1 Ces1e Nagk T23 Gm2382 Ces1e Vps37b Acsm1 Aacs Gm2382 Aacs Prps1l3 Gm2382 Nagk Cdipt Iqgap2Iqgap2 Vps37b Prps1l3 H6pdH6pd Nans Gm2382 Mthfd2 Cdipt Ppp1r7 Dynlt3 Mtmr9 H2- Pgd Nans Mthfd2 Ppp1r7 Dynlt3 Saa3 Cfl2 Mtmr9 H2- Atp1b1 Pgd Saa3 Cfl2 Rpe Dpp4 Atp1b1 Rpe Dpp4 Nans Pigb Vps37a Nans Pigb Cabin1 Vps37a Sptbn2 Tkt Cabin1 Prps1 Tkt Ppp1r11 Vps37c Ldhd Sptbn2 Slc9a6 Prps1 Ppp1r11 Cfl2 Vps37c Slc1a2 Ldhd Cfl2 Myo10 Arfgap2 Slc9a6 Nln Cmas Ylpm1 Marf1 Ppp1r15b Myo10 Chmp2a Arfgap2 Slc1a2 Ephx1 Ylpm1 Ppp1r15b Nln Cmas Ephx1 Marf1 Chmp2a Aldh1l1 Vps54 Farp1 Arap2 Ldlr Ces2e Farp1 Ldlr Chmp1a Aldh1l1 Vps54 Ppp1r35 Arap2 Ces2e Chmp1a Tpm4Tpm1 Ppp1r35 Tkt Tpm4Tpm1 Slc25a10 Rdx Cyp2f2 Acsm5 Tkt Slc25a10 Rdx Copb2 Cyp2f2 Nqo2 Lnpep Acsm5 Nqo2 Plec Dhfr Cnst Copb2 Lnpep Tiprl Acsm3 Plec Dhfr Cyp2f2 Cnst Tiprl Cmas Sod1 Cyp2f2 Diap2 Tuba8 Acsm3 Rdx Actb Cmas Sod1 Wdr81 Diap2 Tuba8 Gne Rdx Wdr81 Uri1 Actb Acsm1 Eml3 Sptan1 Chmp4b Ddost Uri1 Cdipt Gne Ces2g Acsm1 Tuba1a Faah Eml3 Chp1 Sptan1 Mvb12a Arf1 Chmp4b Ddost Dctn6 Gne Slc44a5 Cdipt Ces2g Tuba1a Atp1a1 Tuba1b Ap2a2 Mvb12a Arf1 Faah Chp1 Dhrs7 Dctn6 Slc44a5 H6pd Gne Arfgef1 Rab11fip2 Atp1a1 Enpep Me1 Tuba1b Ap2a2 Eps15 H6pd Dhrs7 Enpep Me1 Arfgef1 Eps15 Rab11fip2 Ppp1r14b Igbp1 Sptbn2 D1 Ppp1r14b Igbp1 Actg1 Sptbn2 D1 Gphn Gcsh Zcchc9 Actg1 Dynlrb1 Gphn Farp1 Mtfmt Glo1 Tpm1 Atp1a1 Cald1 Dera Pgls Gcsh Zcchc9 Dynlrb1 Farp1 Arpc2 Mtfmt Glo1 Tpm1 Tubb2a Atp1a1 Cald1 Slc27a2 Dera Pgls Taldo1 Vps4a Acap2 Arpc2 Tubb2a Slc27a2 Taldo1 Mthfd1 Sptbn1 Vps28 Vps4a Acap2 Arpc2 Sptbn1 Rgn Mthfd1 Arpc5 Vps28 Slc22a1 Dctn5 Arpc2 Gnpnat1 Mthfd1 Bche Rgn Arpc5 Arpc5l Slc22a1 Dctn5 Dctn2 Atox1 Slc37a4 Taldo1 Gnpnat1 Mthfd1 Sacs Bche Tpm3 Dctn2 Arpc5l Ubr4 Nicn1 Snf8 Atox1 Uap1 Dhrs1 Arpc4 Rcan2 L2hgdh Akap11 Styx Lmnb2 Ttll12 Tnnt1 Eml5 Stam2 Slc37a4 Dctn2 Taldo1 Ppp2r4 Synm Tpm3 Mme Pltp Fabp5 Slc12a7 Dctn4 Acsm3 Rbks Gnpnat1 Uap1lUap11 Ldhd Echdc1 Akap1 Chchd6 Ppp2r4 Nckap1 Arpc4 Ubr4 Nicn1 Ttl Sptan1 Mark3 Dnal4 Ehd1 Epn1 Stambp Snf8 Gbf1 Vps4b Arfgap1 Cyth1 Cyth2 Rab22a H2-Bl Slc10a1 Kif5b Dera Rbks Acss3 Uap1lUap11 Akap1 Sacs Igbp1 Ppp1r7 Aspg Dhrs1 Siae Arpc5 Arpc5l Tubb5 Sptbn1 Dst Rab7 Napa Tpm3 Arpc4 Rcan2 L2hgdh Ttll12 Tnnt1 Eml5 Rab11a Stam2 Dctn2 Slc2a2 Slc12a7 Dctn4 Acsm3 Uap1lUap11 Ldhd Echdc1 Chchd6 Akap11 Styx Nckap1 Lmnb2 Ttl Sptan1 Dnal4 Epn1 Stambp Arfgap1 Cyth1 Cyth2 Rab22a H2-Bl Kif5b Rbks Uap1l1 Ppp2r4 Igbp1 Ppp1r7 Arpc5 Arpc5l Synm Sptbn1 Myl6 Mme Pltp Fabp5 Slc2a2 Rbks Gnpnat1 Akap1 Ppp2r4 Arpc4 Dst Mark3 Ehd1 Rab11a Gbf1 Vps4b H2-T22 Rab7 Slc10a1 Napa Tpm3 Dera Acss3 Gcsh Me1 Akap1 Ces2c Aspg Siae Tubb5 Metabolism Genetic information processing Cellular processes Organismal systems Environmental information processing Complement and coagulation cascades

b KEGG complement and coagulation cascades KEGG ribosome KEGG tricarboxylic acid cycle

–2 –2 –2

–4 –4 –4 (protein ) (protein ) (protein) 10 10 10 lo g lo g lo g

–6 –6 –6

–6 –4 –2 –6 –4 –2 –6 –4 –2

log10 (mRNA) log10 (mRNA) log10 (mRNA)

Fig. 4 | Correlations between mRNA and protein levels. a, Proteomaps used to visualize the distributions of mean mRNA (left) and proteins (right) over all FACS gates. Each tile in the map represents a gene; size is proportional to its fraction in the total dataset. Tile colours represent different gene annotations. Genes/proteins that are closer on the maps and share the same colour are closer in function. Visualization was done using the Bionic Visualizations proteomaps (https://bionic-vis.biologie.uni-greifswald.de/, refs. 76–78) Bottom: colour classification key for selected categories. b, Gate- averaged mRNA and protein levels are mildly correlated (Spearman’s r = 0.5). Three KEGG functional classifications with distinct ratios of mRNA and proteins are shown. The red line represents the linear regression. n = 3,051 genes averaged over 5 mice.

enzyme carbamoyl phosphate synthase was ranked first in pro- zonation using immunofluorescence for representative pericen- tein content (0.0682 ± 0.0066), but only 478 in mRNA expression tral and periportal proteins (Supplementary Fig. 4). (2.88 × 10−4 ± 5.4 × 10−5 of cellular transcripts; Fig. 4a). Thus, the The combined measurements of both mRNA and proteins from relative expression levels of mRNA and proteins differ for distinct the same spatially sorted gates enabled a controlled comparison of functional classes. protein and mRNA zonation patterns (Fig. 5b,c). Periportal bias (the difference between expression in the periportal and pericentral gates Zonation patterns of the hepatocyte proteome. We next exam- divided by mean expression) was significantly correlated between ined whether the hepatocyte proteome exhibited zonated patterns. mRNA and proteins, indicating similar mRNA and protein zona- We found that 55% of hepatocyte proteins (1,672 out of 3,051) tion profiles for most genes (Spearman’s r = 0.39, P = 1.45 × 10−110 for were significantly zonated (false discovery rate (FDR) < 0.05, all proteins; r = 0.45, P = 1.71 × 10−79 for highly expressed proteins; Kruskal–Wallis test; Fig. 5a). Periportally and pericentrally Fig. 5b,c). Notably, some genes exhibited discordant zonation of enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) mRNA and proteins. These included genes that were zonated at the pathways largely recapitulated previous zonation studies per- protein but not mRNA level, such as Rbp4, Idh3b, Mrpl43 and genes formed by using RNA7. Bile acid biosynthesis, lipid metabolism that were zonated at the mRNA but not at the protein level, such as and cytochrome P450 xenobiotic metabolism were pericentrally A1cf, Clmn and Lsr (Fig. 5c). The discordant genes also included zonated, while gluconeogenesis, oxidative phosphorylation and Hnf4a, a key hepatocyte transcription factor16,17. The mRNA levels complement and coagulation cascades were periportally zon- of Hnf4a were not zonated, whereas the protein content was higher ated (Supplementary Fig. 3). We validated the measured protein in the periportal gates (Supplementary Fig 4e,f). This periportal

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a GS b GULO 1 4 CYP1A2 Spearman r = 0.39 CYP2E1 Spearman r = 0.45

CYP27A1 2 Hnf4a Hsd17b13 Ftcd S100a1 C8a Aldob

0 Clmn Lsr 0.8 A1cf Idh3b Mrpl43 CYP8B1 Protein periportal bias Rbp4 –2 Gulo CES1E Gstm3

Glul –4 –4 –2 024 0.6 mRNA periportal bias

c Glul Gulo Gstm3 4 2 2 2 1 1

Rbp4 Idh3b Mrpl43 2 1.5 2

0.4 1 1 1 0.5 Protein expression level (normalized to maximum)

A1cf Clmn Lsr 3 2 1.5 2 1 1 C3 1 0.5

S100a1 C8aHnf4a 0.2 2 2 1.5 1 Expression level (normalized to mean) 1 1 0.5 APOA1 Hsd17b13 Ftcd Aldob 2 1.5 1.5 1 1 ALB 1 CPS1 0.5 0.5 ARG1 HSD17B13 12345678 12345678 12345678 12345678 Central Portal Central Portal Central Portal Central Portal CYP2F2 vein node vein node vein node vein node FACS gate mRNA FACS gate Protein

Fig. 5 | A spatial atlas of the hepatocyte proteome. a, Zonation of hepatocyte proteins. Genes are sorted by the zonation profile centre of mass. Representative liver proteins are shown on the left to demonstrate the visualization of zonation profiles. Protein levels were normalized to the maximal level across all FACS gates. b, Periportal bias in expression of mRNA and proteins, calculated as the difference between the two periportal and two pericentral gates, normalized by the mean expression across all gates. Light grey, all matched mRNA and proteins (n = 3,051); dark grey, mRNA and proteins with a minimal expression fraction higher than 10−5 in any of the gates for both mRNA and proteins (n = 1,565). Spearman’s r is indicated for each dataset. The dashed line marks a slope of 1. n = 5 mice c, Expression profiles of mRNAs (grey) and their respective proteins (dark grey). A mean of five mice is plotted. The error bars represent the s.e.m. protein bias is in line with previously reported involvement of our analysis indicates that the majority of proteins and mRNA are HNF4A in periportal repression of Wnt-regulated pericentral similarly zonated, and highlight genes with potential post-tran- genes17–19 and induction of periportally expressed targets20. Indeed, scriptional regulation. we found that in Hnf4a knockout mice21, periportal genes were pref- erentially downregulated compared to wild-type controls, whereas Zonation of hepatocyte miRNA content. We next asked whether pericentral genes did not have preferential differential regulation spatial sorting could be used to explore the regulatory mecha- (Fisher’s exact test P = 1.16 × 10−4; Supplementary Table 5). Thus, nisms that shape hepatocyte zonation. miRNAs are short RNA

Nature Metabolism | www.nature.com/natmetab Articles NATuRe MeTAbOliSm oligonucleotides, roughly 22 base pairs (bp) long, which target included 3,502 interactions between 131 miRNAs and 588 genes. specific mRNAs through Watson–Crick base pairing, leading For each gene, we constructed the cumulative regulating miRNA to increased degradation or decreased translation of target tran- profile by summing up the zonation profiles of all miRNAs with scripts22. Regulation by miRNAs seems to be important in liver a predicted regulatory interaction for the considered target gene development, metabolism and homoeostasis23,24. Notably, miRNA (Supplementary Table 8). We computed the Spearman correlation regulation may impact liver zonation, since mice lacking the between the gene’s mRNA zonation profile and the cumulative miRNA central processing element Dicer in hepatocytes exhibit miRNA zonation profile and compared it to randomized degree- profound changes in zonation patterns25. We reasoned that com- preserving networks (Fig. 7a). bined global measurements of the zonation profiles of miRNAs Our analysis identified 11 genes that were significantly more and mRNAs could identify potential miRNA-target regulatory anti-correlated with their regulating miRNAs compared to random interactions through the detection of miRNA-target pairs with (FDR ≤ 0.2; Fig. 7b, Supplementary Table 8 and Supplementary Fig. 6). anti-correlated expression profiles26. Pericentral target mRNAs included Acat1, which encodes the mito- To this end, we performed miRNA microarray measurements of chondrial enzyme acetyl-CoA acetyltransferase 1, an important spatially sorted hepatocytes from three mice. We detected 302 miR- enzyme in ketone and isoleucine metabolism. Periportal target NAs that were expressed in hepatocytes in all three mice. We further mRNAs included Orm1 and Orm2, encoding alpha-1-acid glyco- focused on 137 miRNAs that were classified as ‘high confidence’ protein 1 and alpha-1-acid glycoprotein 2, respectively; these are in miRBase (v.22, downloaded 30 October 2018)27. Forty-five per secreted plasma carrier proteins that were significantly anti-corre- cent (61 out of 137) of these high-confidence hepatocyte-expressed lated with all of their regulating miRNAs—miR-20a-5p, miR-20b-5p, miRNAs were significantly zonated (FDR ≤ 0.2, Kruskal–Wallis test miR-93-5p and miR-106b-5p (mean Spearman’s r = −0.994 ± 0.011, with Benjamini–Hochberg correction; Fig. 6a). Most zonation pro- Fisher’s method for combining P values of independent tests, files (48 out of 61) were mildly pericentral with a centre of mass P < 10−14; Fig. 7b). Another significantly anti-correlated periportal (COM) between 4 and 4.5, while 7 others showed strong periportal gene was Ly6e, which encodes the protein lymphocyte antigen 6E zonation (COM ≥ 6). We measured the expression of six of the miR- (Supplementary Fig. 6). NAs predicted to be zonated using quantitative PCR with reverse transcription (qRT–PCR), obtaining excellent correspondence with Regulation of Wnt signalling components by miRNA. Wnt the microarray measurements (mean Spearman’s r = 0.70 ± 0.24, is a major factor that shapes hepatocyte zonation34–39. Wnt and Fisher’s method for combining P values of independent tests, R-spondin morphogens are secreted by pericentral liver endothe- P = 1.0 × 10−15; Fig. 6b). lial cells2,13,40–42, resulting in higher pericentral expression of Wnt- The zonated miRNAs included miRNAs previously described as activated genes and lower pericentral expression of Wnt-inhibited playing a role in liver development, metabolism and regeneration. genes7,34. Notably, hepatocyte-specific Dicer knockout mice have In agreement with previous studies28, miR-122-5p, the most abun- perturbed zonation of Wnt-regulated genes, such as Glul and Arg1 dant miRNA in our measurements, comprised 46.5 ± 3.5% of the (ref. 25). This suggests that miRNAs could differentially modulate total miRNA content in hepatocytes. We found that miR-122-5p was hepatocyte Wnt signalling in different lobule zones. To explore periportally zonated, with a 1.15-fold higher expression in the peri- this hypothesis, we analysed the miRNA-target subnetwork portal gates compared to the pericentral gates (P < 0.01, Kruskal– that includes genes associated with Wnt signal processing (see Wallis test; Supplementary Table 6). We confirmed the zonation Methods and Fig. 7c,d). This analysis uncovered several key com- of miR-122-5p with qRT–PCR (Spearman’s r = 0.79; Fig. 6b). ponents of the Wnt network that exhibit zonation in hepatocytes MiR-122-5p was significantly anti-correlated with its targets com- and that have spatially anti-correlated zonated miRNAs. The Wnt pared to randomized genes (Supplementary Fig. 5), indicating receptors Fzd7 and Fzd8 were more highly expressed in pericen- a potential regulatory role in shaping their zonation. Prominent tral hepatocytes, whereas their regulating miRNAs miR149-5p, pericentral miR-122-5p targets (genes that were repressed in their miR-30a-5p, miR-30a-3p, miR-21a-5p, miR-99a-5p and miR- expression in the periportal layers where miR-122 was more abun- 100-5p were more abundant in periportal hepatocytes. In con- dant) included the canonical miR-122-5p target gene Cs, encoding trast, inhibitory components of Wnt signalling, such as Ctnnbip1 citrate synthase, as well as Klf6 and Slc35a4 (ref. 29; Supplementary and Tcf7l1, were periportally zonated. Tcf7l1, also known as Tcf3, Fig. 5). MiR-30a-5p exhibited periportal zonation (periportal to is a transcriptional repressor of Wnt-activated genes that is inac- pericentral ratio of 1.19, Kruskal–Wallis P = 0.007; Fig. 6a and tivated by binding to β-catenin43. This periportally zonated gene Supplementary Table 6). Mtdh, a known target of miR-30a-5p, pre- is anti-correlated with its regulators miR-212-3p, miR-423-5p and viously shown to change in expression in liver tumours30, was peri- miR-5107-5p (Fig. 7d). Ctnnbip1, which encodes β-catenin- inter- central and inversely zonated to its miRNA regulator (Spearman’s acting protein 1, prevents the binding of β-catenin to TCF7L1 and r = −0.81, P = 0.022; Supplementary Table 7). Additional zonated thus its removal and activation of Wnt target genes44. The miR miRNAs included the pericentral miR-103-3p and miR-107-3p and regulators of this periportal gene, miR-188-5p and miR-3102-5p, the periportal miR-802-5p, which have been previously shown to were pericentrally zonated (Fig. 7d). Thus, our analysis high- modulate hepatic glucose sensitivity31,32 (Fig. 6a). In summary, our lights zonated components of hepatocyte Wnt signalling and their measurements revealed profound zonation of key hepatic miRNAs. potential regulation by miRNAs.

Detection of putative miRNA-regulated hepatocyte target genes MiRNA zonation and diseased liver states. Many liver pathologies using zonation profiles. The spatially stratified measurements of exhibit zonated damage, born out of the differential susceptibili- miRNAs and mRNAs could be used to identify potential miRNA ties of periportal and pericentral hepatocytes to different insults4. regulation at the mRNA degradation level. Such regulation would MiRNAs are attractive biomarkers due to their relative stability be manifested in inverse correlations between the zonation profiles and high concentrations in the circulation. Therefore, we sought to of a target mRNA and its regulating miR(s). To identify such inter- explore whether the blood levels of zonated miRNA could be indic- actions, we constructed a miRNA–mRNA regulatory network based ative of such zonated damage. Acetaminophen (APAP) intoxication on predictions from TargetScan (v.7.2)33 (Supplementary Table 7). leads to necrosis of pericentral hepatocytes. We analysed published We included all highly expressed hepatocyte genes and interactions miRNA levels measured in bulk liver and plasma of APAP-treated with high confidence, and filtered out genes that are not predicted mice45 and found that almost all pericentral miRNAs were enriched to be regulated by highly abundant miRNAs. The resulting network in the plasma and depleted in the liver of APAP-treated mice

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a 0

miR-122-5p

–1

miR-22-3p let-7f-5p

miR-30a-5p –2 miR-107-3p miR-125b-5p miR-103-3p miR-99a-5p

(mean expression) miR-31-5p 10 –3 log

miR-125a-5p let-7e-5p miR-31-3p miR-376b-3p miR-100-5p miR-802-5p

–4 miR-137-3p

miR-149-5p

miR-744-5p

34567 Pericentral Zonation COM Periportal

b miR-122-5p miR-31-5p miR-99a-5p 100 5 1.5 1.5 1.5 200 4 Microarra y Microarra y 1 Microarra y 3 1 1 50 100 2 qRT–PCR qRT–PCR qRT–PCR 0.5 0.5 0.5 1

1 2345678 12345678 1 2345678 let-7e-5p miR-376a-3p miR-802-5p 0.4 0.08 0.15 0.3 0.2 0.4 0.3 0.06 Microarra y Microarra y Microarra y 0.1 0.3 0.2 0.2 0.04 0.1 0.2 qRT–PCR qRT–PCR qRT–PCR 0.05 0.1 0.02 0.1 0.1

12345678 1 2345678 1 2345678 FACS gate FACS gateFACS gate

Fig. 6 | Zonated expression of hepatocyte miRNAs. a, Mean expression versus zonation profile centre of mass (COM) for all detected high-confidence miRNAs. Selected miRNAs are labelled. The dashed red lines denote the median of each quantity. The red dots are miRNAs that are significantly zonated (two-sided Kruskal–Wallis test with Benjamini–Hochberg correction, FDR ≤ 0.2). n = 3 mice. b, Validation of hepatocyte miRNA zonation profiles using qRT–PCR. The profiles for both qRT–PCR and microarrays are normalized by the expression levels of miR-103-3p (Spearman’s r = 0.70 ± 0.24). The lines indicate the layer mean over three microarray mouse repeats (red) and the layer mean over three qRT–PCR mouse repeats (blue). The error bars indicate the s.e.m. The discrepancies between qRT–PCR and microarray profiles for let-7e-5p, miR-376a-3p and miR-802-5p may be due to the limited sensitivity of the microarray at low expression levels. n = 3 mice for the microarray and qRT–PCR. relative to controls (P = 0.05, Wilcoxon test; Supplementary Fig. 7), Hepatocellular carcinoma is often associated with the activation whereas periportal miRNAs were not significantly enriched or of the Wnt pathway in hepatocytes38,46. Wnt activity is pericentrally depleted in the plasma versus liver samples (P = 0.43, Wilcoxon test; zonated in the healthy liver. Our study revealed zonated Wnt com- Supplementary Fig. 7). ponents, such as the pericentrally zonated Wnt receptors Fdz7 and

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a Original network Randomized network

miR mRNA + cumulative miR miR mRNA + cumulative miR

r ≈ 0.1 r ≈ 0.8

Shuffle interactions (preserves degree)

r ≈ 0.9 r ≈ –0.7

r ≈ –0.6 r ≈ 0.5

r ≈ 0.8 r ≈ –0.7

Cumulative miR expression r ≈ –0.8 Central Portal r ≈ 0.8 Central Portal vein node vein node Central Portal Target mRNA Lobule layer Central Portal Lobule layer vein node expression vein node Lobule layer Lobule layer

b ×10–4 Acat1 ×10–4 Ly6e ×10–3 Orm1 ×10–3 ×10–3 Orm2 ×10–3 Cumulative miR expression 1 Cumulative miR expression

Cumulative miR profile 4 Cumulative miR profile 6 6 6 2 0.02 0.04 3 4 4 4 2 0.5 0.01 1 0.02 2 2 1 2 mRNA expression mRNA expression mRNA expression mRNA expression

0 0 0 0 0 0 0 0 12345678 12345678 1234 56 78 1234 56 78 FACS gate FACS gate FACS gate FACS gate

c Apc 31-3p 188-5p 423-5p 212-3p 23b-3p 3058-3p Rnf43 361-5p 103-3p 290a-5p Ctnnbip1 125a-3p 21a-5p 551b-5p 125a-5p Lgr4 Tcf7l1 21a-3p Axin2 30a-5p 1198-5p1 98-5p8-5pp 107-3p 3102-5p 27a-3p 669p-3p 7046-3p 219a-5p 30d-5p30d 362-3p Fzd7 Gsk3a 320-3p 192-3p 3069-3p Fzd4 295-5p 5107-5p 338-5p 30e-5p Spearman's r Ctnnb1 671-5p 7a-5p 27b-3p 30c-5p 17-3p 500-3p 6970-5p 149-5p 30e-3p 770-3p Tcf7l2 23a-3p 30b-5p 3085-3p –1 1 122-3p 30a-3p Znrf3 Fzd8 mRNA 100-5p 652-5p 669f-3p 1839-5p 3098-5p 99a-5p miR 350-3p

d miR-30a-5p miR-21a-5p miR-30a-3p miR-149-5p miR-99a-5p miR-100-5p Fzd7 Fzd7 Fzd7 Fzd7 Fzd8 Fzd8 ×10–6 ×10–6 ×10–6 ×10–3 ×10–6 ×10–4 ×10–6 ×10–3 ×10–6 ×10–4 2 8 8 6 0.015 6 0.06 6 1 6 6 6 3 2 4 0.01 4 0.04 4 4 1 4 0.5 4 2 2 2 0.02 2 1 0.005 2 2 2 1 miR expression

12345678 12345678 12345678 123 45678 12345678 123 45678

miR-3102-5p miR-188-5p miR-212-3p miR-423-5p miR-5107-5p miR-1839-5p Ctnnbip1 Ctnnbip1 Tcf7l1 Tcf7l1 Tcf7l1 Znrf3 ×10–5 ×10–3 ×10–5 ×10–4 ×10–5 ×10–3 ×10–5 ×10–4 ×10–5 ×10–3 ×10–6 ×10–4 mRNA expression 2 3 3 1 1 1 1 8 4 4 4 1.5 2 1 2 6 3 3 3 0.5 0.5 0.5 0.5 1 2 4 1 0.5 1 2 2 0.5 1 1 1 2 0 0 1 2345678 12345678 1 2345678 1 2345678 12345678 12345678 FACS gate FACS gate FACS gate FACS gate FACS gate FACS gate

Fig. 7 | Network analysis of miRNA-target interactions. a, Schematic illustration of the algorithm used to infer significant interactions between miRNAs and target genes. b, Zonation profiles of selected genes and their significantly anti-correlated cumulative miRNA profiles. The lines represent the mean of five mice for mRNA (green) and three mice for miRNA (yellow). The error bars represent the s.e.m. c, Regulatory network of hepatocyte-expressed Wnt pathway components and their expressed regulating miRNAs. Edges are coloured according to the correlation between miRNA and target. Edge weight is proportional to the absolute correlation value. n = 3 mice for the miRNA dataset and n = 5 mice for mRNA dataset. d, Selected pairs of miRNAs and regulated Wnt signalling components (green boxes in c). The transcripts of Ctnnbip1, Fzd8, Tcf7l1 and Znrf3 are anti-correlated with most of their regulating miRs, suggesting that miRNAs have a relatively more important role in regulating the expression of these genes in comparison to other genes. The lines represent the means of five mice for mRNA (green) and three mice for miRNA (yellow). The error bars represent the s.e.m.

Fdz8 and the periportally zonated Wnt inhibitors Ctnnbip1 and these miRNAs might be implicated in the carcinogenic process. To Tcf7l1. We found that these components are potentially modulated this end, we analysed the hepatocellular carcinoma dataset of The by zonated miRNA; thus, we hypothesized that perturbations in Cancer Genome Atlas (TCGA; Supplementary Table 9)47. We found

Nature Metabolism | www.nature.com/natmetab NATuRe MeTAbOliSm Articles that periportally zonated miRNAs were downregulated whereas levels to identify potential regulatory interactions that could entail pericentrally zonated miRNA were upregulated (Spearman’s corre- zonated mRNA degradation. This forms an important resource that lation r = −0.29 between the miRNA zonation profile COM and the should be validated in future studies. miRNAs are highly dynamic log(fold change) between tumours and normal tissue, P = 0.0061; along the course of several diseases such as fibrosis, viral infection Supplementary Fig. 8). For example, miR-99a and miR-100, which and liver cancer24,55,56. Spatial sorting could be used to measure potentially inhibit Fzd8 expression in the periportal zones, were the zonation of these miRNAs along the courses of these diseases. downregulated in tumours (log2(fold change) = −1.34 and −0.63, Moreover, our analyses of APAP-treated mice show that plasma respectively; Kruskal–Wallis P = 2.2 × 10−16 and p = 2.6 × 10−4, measurements of zonated miRNAs could potentially be used as bio- respectively). Conversely, miR-93, which potentially inhibits the markers to identify zonated liver damage57,58. Wnt inhibitor Tcf7l1 in the pericentral zone, was upregulated Wnt is a key regulator of hepatocyte zonation2,34,38. The pericen- −20 (log2(fold change) = 1.49, P = 5.4 × 10 ; Supplementary Fig. 8). tral secretion of Wnt morphogens by endothelial cells generates a The anti-correlation between miRNA fold change in hepatocel- zonated external morphogen field, which could explain a signifi- lular carcinoma and its zonation in the healthy liver became even cant fraction of the zonated hepatocyte genes. Our study reveals stronger when focusing on patients without Wnt-activating somatic that in addition to the Wnt signal, the hepatocyte Wnt sensing mutations (Spearman’s r = −0.36, P = 4.5 × 10−4; see Methods). Such and processing machinery also seems to be zonated. We identified increased inverse correlation could indicate that miRNAs may play pericentral zonation of the key Wnt receptors Fzd7 and Fzd8 and a role in activating the Wnt pathway independently of somatic periportal zonation of the Wnt inhibitors Tcf7l1 and Ctnnbip1. This mutations in the Wnt pathway. joins previous reports of periportal zonation of APC, a key Wnt reg- ulator34. Our study further identified miRNAs that regulate these Discussion zonated Wnt components. Thus, miRNAs seem to be upstream of The liver exhibits profound division of labour among hepatocytes Wnt signalling. These results could explain the effects of hepato- that reside at different zones. Thus, understanding and modelling cyte-specific Dicer and β-catenin knockout. While Dicer knockout liver function requires characterization of hepatocyte functions at resulted in perturbed zonation of Wnt targets, β-catenin knockout each lobule coordinate. In this study, we present spatial sorting, a did not substantially alter miRNA levels25. Our finding of decreased generic approach used to isolate large amounts of hepatocytes with expression of miRNAs that may potentially inhibit Wnt receptors high spatial resolution for a broad range of downstream measure- (miR-99a and miR-100) in hepatocellular carcinoma could indicate ment modalities. The approach employs zonated surface markers that Wnt-targeting miRNAs may play a role in the liver carcino- that can be identified by spatially resolved transcriptomic atlases. genic process. We demonstrate applications of this approach for resolving the Our approach allowed us to obtain up to a few hundreds of zonation of hepatocyte proteins and miRNAs. The approach can be thousands of hepatocytes per sorted population. While this amount readily applied to other structured organs and cells types exhibiting is compatible with a broad range of assays, it is insufficient for zonation, including liver endothelial cells13, intestinal enterocytes48 assays that require massively larger amounts of material, such as and kidney cells49,50. The use of endogenous surface markers renders RNA methylation59 and metabolic profiling60. Moreover, since the spatial sorting particularly useful for studying zonation in humans. approach is FACS-based, measuring metabolites, which are labile, Our proteome analysis revealed some notable discordance would be compromised by the substantial incubation periods between the average hepatocyte levels of proteins and mRNAs, involved in the protocol61. Nevertheless, it will be interesting to mostly for genes encoding secreted proteins (Fig. 4). In contrast, apply spatial sorting to explore additional zonated hepatocyte fea- we found that protein zonation profiles highly overlap those of tures, including chromatin modifications, DNA methylation, three- mRNAs. These results argue for a predominance of spatial regula- dimensional chromosomal conformations, DNA mutation spectra tion of hepatocyte protein levels via transcription or mRNA stability, and chromosomal aberration. Such measurements could resolve rather than through translational control or protein stability. Hnf4a, hepatocyte cell identity, regulatory mechanisms and susceptibility which encodes a key hepatic transcription factor, was among the to damage in each zone. small group of genes for which protein and mRNA zonation pro- files were discordant. Hnf4a mRNA was expressed in a non-zonated Methods manner, whereas its protein levels were periportally zonated. This Animal experiments. Mouse experiments were approved by the Institutional fits with previous reports of periportal expression of Hnf4a hepato- Animal Care and Use Committee of the Weizmann Institute of Science and cyte target genes16,18–20. Notably, Hnf4a is a transcriptional activator performed in accordance with institutional guidelines. Te sorting experiments 51 were conducted on fve 3-month-old C57BL/6JOlaHsd male mice obtained from of miR-122 (ref. ), the most abundant liver-expressed miR, which Envigo. Mice were fed ad libitum and were kept in a reverse light–dark cycle. we also found to be periportally zonated. Due to the sensitivity limi- Mice were anaesthetized with ketamine (100 mg kg−1) and xylazine (10 mg kg−1) tations of mass spectrometry proteomics, our proteomic measure- dissolved in 1× PBS and injected intraperitoneally 6–9 h afer lights of (Zeitgeber ments did not include low-abundance proteins, including other key time 18–21). liver transcription factors, which may exhibit higher levels of post- For the imaging experiments, the livers of the 3-month-old C57BL/6JOlaHsd male mice were collected and fixed in cold paraformaldehyde for 3 h at 4 °C transcriptional regulation. followed by overnight fixation in cold paraformaldehyde + 30% sucrose at 4 °C Recent studies have begun to develop in silico multi-scale models while revolving. Livers were embedded in optimal cutting temperature (Tissue-Tek, for predicting the liver’s response to stimulation by metabolites and VWR) the next morning. Blocks were kept at −80 °C. xenobiotics52–54. These models consider multiple units representing hepatocytes at different zones that exchange materials and process Immunofluorescence of CD73 and E-cadherin. Optimal cutting temperature- them through individualized metabolic networks, thus model- embedded mouse liver blocks were sectioned into 7 μm thick slices. Slices were ling the polarized blood perfusion throughout the lobule. Future fixed with cold methanol for 20 min. After three 5 min washes with PBST (1× PBS, 1% bovine serum albumin (BSA) + 0.1% Tween), sections were permeabilized incorporation of the zonated levels of enzymes into such models by 10 min incubation at room temperature with PBSTX solution (1× PBS, 0.25% could increase their precision and better capture in vivo fluxes. Our Triton-X100 and 1% BSA). Slices were then washed again as before and incubated proteomic map provides such detailed zonation of key enzymes for 1 h at room temperature with blocking solution (1× PBS, 0.1% Tween and 5% (Supplementary Table 3). goat/normal horse serum). Slices were next incubated with the antibody solution (blocking solution with 1:50 antibody in a total reaction volume of 150 μl) at 4 °C Our work provides a global spatial atlas of miRNA zonation, overnight. Antibodies used were Alexa Fluor 647 rat anti-mouse CD73 (catalogue identifying key hepatocyte zonated miRNAs such as miR-122-5p no. 561543; BD Biosciences) and Alexa Fluor 555 mouse anti-E-cadherin and miR-30a-5p. We used the combined miRNA and target mRNA (catalogue no. 560064; BD Biosciences). On the next day, slices were washed with

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PBST three times. Nuclei were stained with 4,6-diamidino-2-phenylindole (DAPI; compensation was corrected manually. To collect eight populations, each enriched 1:100 in PBS, 10 min). Imaging of the liver porto-central axis was performed with spatially stratified hepatocytes with equal viability and ploidy levels, events on a Nikon Ti-E inverted fluorescence microscope with a 100× oil-immersion were screened through the following five nested gates (Fig. 3a,b and Supplementary objective and a Pixis 1024 charge-coupled device camera (Photometrics) using the Fig. 1b–d): (1) hepatocyte gates from all events—set by plotting forward side MetaMorph software (v.7.77.11.0) in scan stage option. scatter area (FSC-A) against side scatter area (SSC-A) and excluding large clusters The Z-projected images of lobule scans (8 scans, 3 mice) were analysed. and small debris; (2) singlets FSC—set by excluding the margins of FSC-A and Membrane segments of hepatocytes were measured for the intensity of Alexa FSC width plot; (3) singlets SSC—excluding the upper margins of SSC width when Fluor 555 (E-cadherin) and Alexa Fluor 647 (CD73). Background, set as the plotted against SSC-A; (4) live cell gates according to the Zombie Green-Alexa paired cytoplasmic intensity for each membrane signal, was subtracted. Segments Fluor 488− cells, comparable to unstained cells; (5) hepatocytes only, by depleting were then binned into eight groups representing eight lobule layers (1 marks the CD31 and CD45 (markers of NPCs); and (6) tetraploid hepatocytes, inferred by pericentral-most layer, and 8 marks the periportal-most layer), according to their Hoechst histogram (Fig. 3a,b and Supplementary Fig. 1c,d). Hepatocyte size and radial distance from the central vein. The median intensity of the segments overall protein content scale with ploidy64, thus creating spurious correlations from each lobule layer was calculated and averaged over the different lobules between the zonated surface markers (Supplementary Fig. 1c,d). Sorting without (Fig. 2b,c). Values were scaled from 0 to 1 and the plot was smoothed with a ploidy stratification would result in the inclusion of hepatocytes from different sliding window of 3. lobule layers, reducing spatial accuracy (Supplementary Fig. 1c,d). We then plotted PE intensity for E-cadherin staining and APC intensity Immunofluorescence of aldolase B and glutamine synthetase. for CD73 staining. Positively stained cells were determined by measuring the Immunofluorescence of aldolase B (catalogue no. PA5-30218; Thermo Fisher intensities of unstained cells. The highest intensity for unstained cells was the Scientific) and glutamine synthetase (catalogue no. MA5-27749; Thermo Fisher threshold for positively stained cells. Each population, CD73+ and E-cadherin+, Scientific) was performed in a similar fashion to E-cadherin and CD73; however, was further gated to four equal subpopulations, representing graded intensities secondary antibodies were needed after overnight incubation with primary of the marker. Thus, subpopulations 1, 2, 3 and 4 had an equal amount of events, antibodies. Slides were incubated for 2 h at room temperature with secondary 1 had the highest APC-CD73 intensity while 2, 3, 4 had gradually decreasing antibodies before staining with DAPI. For aldolase B, we used 1:500 goat anti- intensities of APC. Likewise, subpopulations 5, 6, 7 and 8 were equally distributed, rabbit immunoglobulin G (IgG) (H+L) crossadsorbed secondary antibody 8 having the highest PE-E-cadherin intensity while 7, 6 and 5 had gradually conjugated to cyanine 3 (catalogue no. A10520: Thermo Fisher Scientific). For decreasing PE intensities. Populations 4 and 5 contained cells from a below positive glutamine synthetase, we used 1:500 goat anti-mouse IgG (H+L) crossadsorbed intensity threshold, to accurately resemble mid-lobule hepatocytes, where both secondary antibody conjugated to cyanine 3 (catalogue no. A10521; Thermo Fisher CD73 and E-cadherin abundances are very low (Fig. 2). All gates were set for each Scientific). of the five experiments independently, with a wide overlap. Ten thousand hepatocytes from each gate were sorted using the Dynabeads Immunofluorescence of HNF4A. HNF4A antibody staining was done according mRNA DIRECT Micro Purification Kit (Invitrogen) for RNA-seq. After sorting, to a previously published protocol62. Paraffin-embedded liver blocks were sectioned cells were spun down and frozen at −80 °C until processing. One hundred into 10 μm thick slices. Slides were deparaffinized and rehydrated, followed by thousand hepatocytes from each population were collected into FACS buffer and methanol incubation for 5 min. Slides were then incubated in citrate buffer (pH resuspended twice with PBS to wash away serum proteins. Pellets were flash-frozen 5.8–6.0) for 30 min at 100 °C for heat-induced epitope retrieval. Blocking of non- and sent to be processed and measured using mass spectrometry proteomics (The specific binding sites was done by 1 h incubation with PBS, 10% BSA and 0.3% Smoler Protein Research Center). An additional 50,000 cells were collected for Triton-X100, after which slides were incubated overnight with HNF4A antibody miRNA microarray. Total RNA was isolated using Direct-zol RNA MicroPrep kit (catalogue no. PP-H1415-00; R&D Systems) in a dilution of 1:350 in blocking (Zymo Research). solution at 4 °C. Slides were incubated for 2 h in 1:700 donkey anti-Mouse IgG (H+L) highly crossadsorbed secondary antibody conjugated to Alexa Fluor 594 RNA-seq. Ten thousand hepatocytes from each sorted population were collected for (catalogue no. A-21203; Thermo Fisher Scientific) with 1:1,000 DAPI. library preparation. Cells were sorted into lysis buffer supplied with the Dynabeads mRNA Purification Kit (catalogue no. 61006; Invitrogen). RNA was extracted Liver perfusions and hepatocytes dissociation. Once mice had been according to the protocol provided with the kit: 2 μl of the extracted mRNA from anaesthetized, their livers were perfused as described previously63, with a few each sample were used for the libraries. Library preparation was done according adjustments. A 27 G syringe connected to the perfusion line and pump was to the mcSCRB-seq protocol65. The complementary DNA was pre-amplified with inserted into the vena cava; 25 ml of pre-warmed to 37 °C EGTA buffer followed by 10–15 cycles, depending on the cDNA concentration indicated by qRT–PCR quality 25 ml of pre-warmed to 37 °C enzyme buffer solution (EBS) with 2.3 U of Liberase control; 2 ng of the amplified cDNA was converted into the sequencing library Blendzyme 3 recombinant collagenase (Roche) were cannulated into the vena with the Nextera XT DNA Library Preparation Kit (catalogue no. FC-131-1024; cava. Shortly after the beginning of the perfusion, the portal vein was cut to allow Illumina), according to the protocol supplied. Quality control of the resulting drainage of the blood. libraries was performed with a High Sensitivity DNA ScreenTape Analysis system After perfusion of 10 ml EGTA and 15 ml of enzyme solution, livers were (catalogue no. 5067-5584; Agilent Technologies). Libraries were loaded with a explanted into a Petri dish with 25 ml of pre-warmed EBS and gently minced using concentration of 2.2 pM on 75-cycle high-output flow cells (catalogue no. FC-404- forceps. Dissociated liver cells were collected and filtered through a 100 μm cell 2005; Illumina) and sequenced on a NextSeq 500 (Illumina) with the following cycle strainer. Cells were spun down at 30g for 3 min at 4 °C to obtain the hepatocyte- distribution: 8 bp index1, 16 bp read1, 66 bp read2 (no index2 needed). A total of 40 enriched pellet. Pellet was resuspended in 25 μl cold EBS. libraries (8 sorted populations for 5 different mice) were sequenced.

Cell staining. To discard dead hepatocytes, 22.5 ml Percoll (Sigma-Aldrich) Sequencing analysis pipeline. Illumina output files were demultiplexed with mixed with 2.5 ml 10× PBS was added to the cells. Cells were centrifuged at bcl2fastq v.2.17; the resulting FASTQ files from the mRNA sequencing experiments 600 r.p.m. for 10 min. The supernatant containing the dead cells was aspirated were analysed with the zUMIs pipeline66. Using STAR (v.2.5.3a), reads were aligned and cells were resuspended in pre-warmed Hoechst buffer (DMEM + 10% to a transcriptome index of the GRCm38 (release 84; Ensembl) and exonic unique FCS + 10 mM HEPES). After counting, the concentration was adjusted to 2 × 106 molecular identifier counts per million were calculated using the pipeline default cells in 1 ml. To determine the ploidy of hepatocytes, DNA was stained with settings and trimmed mean of M-values normalization67 implemented in edgeR Hoechst (Thermo Fisher) (15 μg ml−1). Reserpine (5 μM) was also supplemented (v.3.14.0)68; 14,027 transcripts were identified in the experiment involving the 40 to prevent Hoechst expulsion from the cells. Cells were incubated for 30 min libraries. Data were further normalized by dividing each sample by its sum of counts at 37 °C. Hepatocytes were centrifuged for 5 min at 1,000 r.p.m. at 4 °C and the per million. Two out of the 40 libraries failed to reach over 200,000 reads and were supernatant was discarded. Next, cells were stained with Alexa Fluor 488 Zombie discarded (m2_2_cpm and m3_5_cpm samples in Supplementary Table 2). Green (BioLegend) to later enable the detection of viable cells by FACS. Cells were resuspended in cold PBS in a concentration of 106 cells in 100 μl. Zombie Green Mass spectrometry. Forty samples (five mice, eight populations each) were was added at a dilution of 1:500. Cells were kept in a rotator in the dark at room digested by trypsin and analysed with liquid chromatography–tandem mass temperature for 15 min. After spinning down (1,000 r.p.m. for 5 min at 4 °C), cells spectrometry on a Q Exactive Plus Hybrid Quadrupole-Orbitrap Mass were resuspended in FACS buffer (2 mM EDTA, pH 8, and 0.5% BSA in 1× PBS) Spectrometer (Thermo Fisher Scientific). The data were analysed with MaxQuant at a concentration of 106 cells in 100 μl. Cells were stained with the following v.1.5.2.8 (ref. 69) against the mouse Uniprot database. Data were quantified using BioLegend antibodies at a dilution of 1:300: PE-anti-mouse/human CD324 the same software. We retained proteins with a FDR < 0.01 in at least 2 samples E-cadherin (catalogue no. 147304); APC anti-mouse CD73 (catalogue no. 127210); in one of the 8 groups, identified by at least 2 peptides across all samples; 3,210 PE/Cy7 anti-mouse CD31 (catalogue no. 102418); and APC/Cyanine7 anti-mouse proteins were identified. For each sample, label-free quantification intensities for CD45 (catalogue no. 103116). FcX blocking solution (BioLegend) was added at a each peptide were normalized by the sum of all intensities, yielding the expression dilution of 1:50. fraction out of the total protein detected.

Flow cytometry and cell sorting. Cells were sorted by SORP-FACSAria II sorter Analysis of potential NPC representation. Although we used negative selection (BD Biosciences) using a 130 μm nozzle and 1.5 natural density filter. Laser with surface markers for endothelial (CD31) and immune cells (CD45), we

Nature Metabolism | www.nature.com/natmetab NATuRe MeTAbOliSm Articles computationally validated that there was no significant presence of NPCs in our measurements previously reconstructed using spatially resolved single-cell sorted populations. To this end, we compiled a gene expression dataset of nine transcriptomics7 (Fig. 3c), we computationally estimated the relative abundances of major liver cell types from previous publications13,70, including endothelial cells, the different lobule layers in each of the FACS gates. To this end, we implemented T cells, plasmacytoid dendritic cells, Kupffer cells, liver capsule macrophages, Cibersort (https://cibersort.stanford.edu/)71. We extracted a gene signature list B cells, neutrophils, hepatocytes13 and cholangiocytes70. We filtered the dataset for each layer from the single-cell RNA-seq data7. A total of 17 genes with a mean to include only genes with a transcriptome fraction of at least 10−5 in at least expression > 5 × 10−5, a zonation FDR < 0.01 and dynamic range of at least tenfold one cell type, and which were present in our spatially sorted hepatocyte RNA- between the mean of the two periportal layers and the mean of the two pericentral seq data, resulting in 9,805 expressed genes. We next identified the top 100 layers were used for the analysis. The means of five mice for the zonation profiles marker genes for each of the nine cell types, defined as having the largest ratio of these genes across the eight sorted gates were used as the mixed populations between their expression in a given cell type and the maximum expression dataset. The relative abundances of each of the nine layers in each of the eight over all other cell types (Supplementary Table 1). The summed expression of sorted populations was calculated (with the ‘disable quantile normalization’ option the marker genes, which we termed the cell types’ ‘signature’, was calculated for ticked). Figure 3c shows the mean expression in each FACS gate over five mice both the transcriptomic and proteomic data of our sorted populations. In the (blue) and the mean expression in single-cell RNA-seq data7, weighted by the transcriptomic data, the hepatocyte signature made up 15.7 ± 1% of the spatially relative abundances of each layer in each FACS gate (yellow). sorted populations, while each of the other cell types’ signatures comprised only 0.075–0.27% of the transcriptomic signature matrix in each FACS gate, indicating Comparing proteins and RNA. Out of the 3,210 proteins (Supplementary Table 3) a 100-fold ratio between unique hepatocyte signature contribution and that of detected using mass spectrometry and 14,027 mRNAs (Supplementary Table 2) other cell types. Importantly, there were no significant differences in the levels of detected using RNA-seq, 3,051 were found in both datasets (Supplementary the cell type signatures across the spatially sorted populations (Kruskal–Wallis Table 4). The median expression fraction of five mice was calculated for each P = 0.99). In the proteomic data, the hepatocyte signature made up 4.5 ± 0.8% of gate in each measurement. We produced scatterplots showing the averages over the total protein content, while each of the other cell-type signatures comprised all gates of the eight mRNA and eight protein medians for every gene and found only 0.0004–0.4113% of the protein content. Likewise, there were no significant a Spearman correlation of r = 0.50 (0.48–0.50 for each gate independently). To differences in the levels of the proteomic cell type signatures across the spatially better characterize mRNA and protein ratios in different KEGG pathways72, we sorted populations (Kruskal–Wallis P = 1). plotted a regression line of protein by mRNA. The residual of the proteins from the regression line was calculated and grouped according to KEGG pathways (Fig. 4b Calculating zonation of Hnf4a targets. We used the data from Holloway et al.21 and Supplementary Fig. 2b). for differentially expressed genes in male mice with Hnf4α knockout compared to wild-type male mice. We extracted a unique list of these genes and calculated the Computing zonation. For each of the 3,051 common proteins and mRNAs, a Benjamini–Hochberg FDR to identify significantly differentially expressed genes, Kruskal–Wallis test was performed to check for variability between different set to have an FDR < 0.01. Those genes were intersected with our spatial sorting sorted gates (n = 40 populations, 5 mice in each of the 8 gates, d.f. = 37). To correct RNA-seq data, resulting in 1,166 genes. We next grouped the genes according to for multiple hypotheses, we performed the Benjamini–Hochberg procedure to the following categories: genes were considered downregulated or upregulated if obtain the FDR for each hypothesis. We classified proteins as zonated if they their knockout/wild-type log2(fold change) was smaller than −1 or greater than had an FDR < 0.05; 1,672 were significantly zonated. To produce the protein 1, respectively; genes were considered pericentral/periportal, according to our zonation heatmap (Fig. 5a), we first removed all proteins with a median of label- spatial sorting RNA-seq data, if their zonation COM was smaller or larger than 4.5, free quantification = 2 (ref. 18) in any of the eight gates (479 proteins). Next, we respectively. These criteria formed 4 groups: upregulated pericentral genes (296 normalized all protein profiles to their maximum across all FACS gates and sorted genes); upregulated periportal genes (123 genes); downregulated pericentral genes them by their COM (Fig. 5a). (348 genes); and downregulated periportal genes (245 genes). We used Fisher’s exact test to identify a non-random association between differential expression and Microarray data. Only miRNAs that were annotated as ‘high confidence’ in zonation under Hnf4a knockout (P = 1.2 × 10−4). miRBase v.22 (downloaded 30 October 2018) were kept for analysis. The raw signal for each miRNA in each FACS gate and in each array was normalized by the total miRNA microarrays. Total RNA (100 ng), isolated from bulk populations of signal per gate per array. Only miRNAs present in all three biological replicates 50,000 spatially sorted hepatocytes (n = 3) per FACS gate, was labelled with cyanine were retained for further analysis and their initial normalized signal was averaged 3 during transformation into cDNA using an miRNA Labelling Kit (Agilent over all arrays. Finally, the averaged signal was divided again by the total signal Technologies) and Spike Kit (Agilent Technologies). cDNA was hybridized to the in each gate. (This operation amounted to dividing by a number very close to Mouse miRNA Microarray, release 21.0, 8 × 60 K (v.21) microarray slides (Agilent 1, since only miRNAs with very low expression were not present in some of the Technologies) according to the Agilent miRNA Hybridization Kit protocol (Agilent replicates.) MiRNA zonation was inferred using the Kruskal–Wallis test (for each Technologies) and scanned using a G2505B array scanner (Agilent Technologies). miR, comparison of 8 gates with each having 3 replicates, d.f. = 21), and applying a Data were extracted using the Feature Extraction Software (v.10.7.3.1, Agilent Benjamini–Hochberg correction on the P values obtained from the Kruskal–Wallis Technologies) with default parameters. test. MiRNAs with an FDR ≤ 0.2 were classified as zonated. qRT–PCR. The total RNA isolated from bulk populations of 50,000 spatially Differential zonation of miR-122-5p targets. The targets of miR-122-5p were sorted hepatocytes (n = 3) per FACS gate was diluted to 5 ng µl−1 and cDNA was taken from Tsai et al.29; 146 of the targets listed were expressed in our liver zonated reverse-transcribed using the miRCURY LNA RT Kit (catalogue no. 339340; transcriptome data. The mean COM was calculated for these targets and for 1,000 QIAGEN), according to the manufacturer’s instructions, on a ProFlex PCR random samplings (with replacement) of 146 liver-expressed genes (genes with System (Applied BioSystems). Plates were prepared using the miRCURY LNA maximal expression over all gates that was at least 4 × 10−6 of the transcriptome). SYBR Green PCR Kit (catalogue no. 339346; QIAGEN) with custom miRCURY We performed a Wilcoxon rank-sum test for the COMs of the target genes versus LNA PCR primers (catalogue no. 339306; QIAGEN; Supplementary Table 10). the COMs of randomly sampled genes, yielding P = 0.018. Each 10 µl reaction volume contained 5 µl 2× miRCURY SYBR Green Master Mix, 0.5 µl 6‐carboxy‐X‐rhodamine reference dye, 1 µl PCR primer mix, 0.5 µl Analysis of APAP-induced liver injury data. Mature sequence suffixes (‘-3p/- RNase-free water and 3 µl of cDNA sample diluted 1:60. qRT–PCR reactions 5p’) were removed from the miRNA names in the dataset from Wang et al.45 and and measurements were performed on a StepOne Real-Time PCR System names were matched with our miRNA zonation data, after merging miRNAs with (catalogue no. 4376357; Thermo Fisher Scientific) according to the manufacturer’s duplicate names. Pericentral miRNAs were defined as those with a COM ≤ 4.5 instructions. Correlations between qRT–PCR and microarray measurements were and Kruskal–Wallis FDR ≤ 0.2, whereas periportal miRNAs had a COM > 4.5 calculated on a mouse-by-mouse basis. and Kruskal–Wallis FDR ≤ 0.2. A Wilcoxon’s rank-sum test was calculated for the ratios log2(treatment/control) of all detected pericentral miRNAs in the plasma Centre-of-mass calculation. The COM of an expression profile x (spread over versus in the liver. z = 1:8 FACS gates) was calculated as: 8 Analysis of TCGA hepatocellular carcinoma data. TCGA-hepatocellular z 1 z ´ xz COM x ¼ 1 carcinoma data (level 3 miRNA and mRNA-seq datasets, not RSEM-normalized) ð Þ¼ 8 ð Þ P z 1 xz were downloaded using the RTCGA package https://rtcga.github.io/RTCGA/, ¼ v.1.5.1). To match our microarray miRNA nomenclature, which can inform P This formula yields a COM∈[1,8] number that shows around which gate most from which mature miRNA the signal came from (that is, the ‘-3p/-5p’ suffixes of the expression is distributed. to the miRNA names), and the RNA-seq data, which do not have this specificity, names and expression values were merged between degenerate miRNA names. Comparing bulk mRNA with published single-cell RNA-seq. Spatial sorting Specifically, ‘-3p/-5p’ suffixes and genomic locus variants (indicated by additional produces subpopulations of hepatocytes that are enriched for specific lobule digits after the canonical miRNA number) were removed from the miRNA names layers; however, each FACS gate includes several lobule layers. Thus, to compare and the expression values of miRNAs with the resulting identical name were the bulk mRNA measurements of the FACS-gated subpopulations to the zonation summed. The resulting TCGA data included the values of 1,046 miRNAs over

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372 tumour samples and 50 normal samples. For each miRNA, we computed the Received: 20 January 2019; Accepted: 8 August 2019; log2 ratio of the median expression levels in the tumour and normal samples and Published: xx xx xxxx examined the Spearman correlations of the log2 ratios and the zonation profile COM for the miRNAs that were included in our spatial sorting study. To examine the magnitude of fold change in miRNA expression independently of Wnt pathway References mutations, we stratified the TCGA data by patients’ mutation state and removed 1. Hoehme, S. et al. Prediction and validation of cell alignment along from the analysis all patients with mutations in at least one of the genes APC and microvessels as order principle to restore tissue architecture in liver CTNNB1, and all FZD genes (FZD1–FZD10). regeneration. Proc. Natl Acad. Sci. USA 107, 10371–10376 (2010). 2. Wang, B., Zhao, L., Fish, M., Logan, C. Y. & Nusse, R. Self-renewing diploid + MiRNA-target network construction, randomized networks and genes–miRNA Axin2 cells fuel homeostatic renewal of the liver. Nature 524, 180–185 (2015). anti-correlation. All miRNA-target interaction predictions were downloaded 3. Colnot, S. & Perret, C. in Molecular Pathology of Liver Diseases (ed. Monga, from TargetScanMouse v.7.2 (ref. 33) (data released in August 2018, downloaded P. S.) 7–16 (Springer, 2011). 24 October 2018), including conserved and non-conserved sites. Predicted 4. Ben-Moshe, S. & Itzkovitz, S. Spatial heterogeneity in the mammalian liver. edges were filtered for only liver-expressed miRs, annotated ‘high confidence’ in Nat. Rev. Gastroenterol. Hepatol. 16, 395–410 (2019). miRBase v.22, weighted context++ score percentile ≥ 95 and genes expressed with 5. Gebhardt, R. Metabolic zonation of the liver: regulation and implications for maximum fraction (over gates) of total transcriptome ≥4 × 10−6). The resulting liver function. Pharmacol. Ter. 53, 275–354 (1992). network included 33,672 interactions between 131 miRNAs and 6,650 genes. For 6. Jungermann, K. & Keitzmann, T. Zonation of parenchymal and nonparenchymal metabolism in liver. Annu. Rev. Nutr. 16, 179–203 (1996). each gene g we constructed the cumulative expression profile Mg(z) of all miRNAs 7. Halpern, K. B. et al. Single-cell spatial reconstruction reveals global division μi(z),i∈{1,2,…,Ng},z = {1,…8} predicted to target it: of labour in the mammalian liver. Nature 542, 352–356 (2017). Ng 8. Lindros, K. O. & Penttilä, K. E. Digitonin-collagenase perfusion for efcient M z μ z 2 g i ð Þ separation of periportal or perivenous hepatocytes. Biochem. J. 228, ð Þ¼ i 1 ð Þ X¼ 757–760 (1985). 9. Quistorf, B., Grunnet, N. & Cornell, N. W. Digitonin perfusion of rat liver. A

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Ziv and the Smoler Proteomics Center (Technion) for Int. 26, 101–111 (1984). performing the liquid chromatography–tandem mass spectrometry and analysing 51. Xu, H. et al. Liver‐enriched transcription factors regulate microRNA‐122 that the results; and D. Pilzer and the Genomic Technologies Unit (Weizmann Institute of targets CUTL1 during liver development. Hepatology 52, 1431–1442 (2010). Science) for performing the miRNA microarray measurements. We thank all members 52. Berndt, N., Horger, M. S., Bulik, S. & Holzhütter, H.-G. A multiscale of the laboratory for valuable comments. S.I. is supported by the Henry Chanoch Krenter modelling approach to assess the impact of metabolic zonation and Institute for Biomedical Imaging and Genomics, The Leir Charitable Foundations, the microperfusion on the hepatic carbohydrate metabolism. PLoS Comput. Biol. Richard Jakubskind Laboratory of Systems Biology, the Cymerman-Jakubskind Prize, 14, e1006005 (2018). The Lord Sieff of Brimpton Memorial Fund, the I-CORE programme of the Planning 53. Godoy, P. et al. Recent advances in 2D and 3D in vitro systems using primary and Budgeting Committee (grant no. 1902/12), the Israel Science Foundation (grant hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells no. 1486/16), the Broad Institute-Israel Science Foundation (grant no. 2615/18), the and their use in investigating mechanisms of hepatotoxicity, cell signaling and European Research Council (ERC) under the European Union’s Horizon 2020 research ADME. Arch. Toxicol. 87, 1315–1530 (2013). and innovation programme (grant no. 768956), the Bert L. and N. Kuggie Vallee 54. Holzhütter, H.-G., Drasdo, D., Preusser, T., Lippert, J. & Henney, A. M. Te Foundation, the Howard Hughes Medical Institute (HHMI) International Research virtual liver: a multidisciplinary, multilevel challenge for systems biology. Scholar Award (grant no. 55008734), The Wolfson Family Charitable Trust (grant no. Wiley Interdiscip. Rev. Syst. Biol. Med. 4, 221–235 (2012). 21376) and the Edmond de Rothschild Foundations. 55. Jopling, C. L., Yi, M., Lancaster, A. M., Lemon, S. M. & Sarnow, P. Modulation of hepatitis C virus RNA abundance by a liver-specifc Author contributions microRNA. Science 309, 1577–1581 (2005). K.B.H. and S.I. conceived the study. S.B.M. and S.I. designed the experiments. S.B.M. 56. Roderburg, C. et al. Micro-RNA profling reveals a role for miR-29 in human prepared all the samples. S.B.M. and Y.S. analysed the data. A.E.M. contributed to the and murine liver fbrosis. Hepatology 53, 209–218 (2011). data analysis. R.M. and T.V. assisted with the immunofluorescence experiments. K.B.H. 57. Mitchell, P. S. et al. Circulating microRNAs as stable blood-based markers for contributed to establishing the methodology. S.I. supervised the study. S.B.M., Y.S. and cancer detection. Proc. Natl Acad. Sci. USA 105, 10513–10518 (2008). S.I. wrote the manuscript. All authors reviewed the manuscript and provided input. 58. Farid, W. R. et al. Hepatocyte‐derived microRNAs as serum biomarkers of hepatic injury and rejection afer liver transplantation. Liver Transpl. 18, 290–297 (2012). Competing interests 59. Dominissini, D. et al. Topology of the human and mouse m6A RNA The authors declare no competing interests. methylomes revealed by m6A-seq. Nature 485, 201–206 (2012). 60. Hirayama, A. et al. Quantitative metabolome profling of colon and stomach Additional information cancer microenvironment by capillary electrophoresis time-of-fight mass Supplementary information is available for this paper at https://doi.org/10.1038/ spectrometry. Cancer Res. 69, 4918–4925 (2009). s42255-019-0109-9. 61. Llufrio, E. M., Wang, L., Naser, F. J. & Patti, G. J. Sorting cells alters their redox state and cellular metabolome. Redox Biol. 16, 381–387 (2018). 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Nature Metabolism | www.nature.com/natmetab nature research | reporting summary

Corresponding author(s): Shalev Itzkovitz

Last updated by author(s): Jul 25, 2019 Reporting Summary Nature Research wishes to improve the reproducibility of the work that we publish. This form provides structure for consistency and transparency in reporting. For further information on Nature Research policies, see Authors & Referees and the Editorial Policy Checklist.

Statistics For all statistical analyses, confirm that the following items are present in the figure legend, table legend, main text, or Methods section. n/a Confirmed The exact sample size (n) for each experimental group/condition, given as a discrete number and unit of measurement A statement on whether measurements were taken from distinct samples or whether the same sample was measured repeatedly The statistical test(s) used AND whether they are one- or two-sided Only common tests should be described solely by name; describe more complex techniques in the Methods section. A description of all covariates tested A description of any assumptions or corrections, such as tests of normality and adjustment for multiple comparisons A full description of the statistical parameters including central tendency (e.g. means) or other basic estimates (e.g. regression coefficient) AND variation (e.g. standard deviation) or associated estimates of uncertainty (e.g. confidence intervals)

For null hypothesis testing, the test statistic (e.g. F, t, r) with confidence intervals, effect sizes, degrees of freedom and P value noted Give P values as exact values whenever suitable.

For Bayesian analysis, information on the choice of priors and Markov chain Monte Carlo settings For hierarchical and complex designs, identification of the appropriate level for tests and full reporting of outcomes Estimates of effect sizes (e.g. Cohen's d, Pearson's r), indicating how they were calculated

Our web collection on statistics for biologists contains articles on many of the points above. Software and code Policy information about availability of computer code Data collection For RNA seq analysis, we used BCL2fasq tool (Illumina), STAR (2.5.3a) for alignment and zUMIs for quantification. For proteomics analysis, we used MaxQuant (1.6.0.16) for identification and quantification. For miRNA microarrays analysis, we used Agilent Feature Extraction software. we used BD FACSDiva™ Software (BD Biosciences-US) for sorting and MetaMorph software for microscope image acquisition.

Data analysis Data analysis Data were analyzed using MATLAB (R2018) and RStudio (v1.2, using R v3.5). R packages used for analysis are "dplyr",tidyr","biomaRt" and "edgeR". Additional tools employed are mfinder, CIBERSORT and Proteomap. For manuscripts utilizing custom algorithms or software that are central to the research but not yet described in published literature, software must be made available to editors/reviewers. We strongly encourage code deposition in a community repository (e.g. GitHub). See the Nature Research guidelines for submitting code & software for further information. Data Policy information about availability of data All manuscripts must include a data availability statement. This statement should provide the following information, where applicable: - Accession codes, unique identifiers, or web links for publicly available datasets October 2018 - A list of figures that have associated raw data - A description of any restrictions on data availability

RNA sequencing data that support the findings of this study have been deposited in NCBI Sequence Read Archive (SRA) with the BioProject accession code PRJNA556572, and the SRA identifiers SAMN12360372- SAMN12360382. Supplementary Table 2 summarizes the UMI counts per million for each sample. Supplementary Table 11 summarizes the zUMI barcodes used per each sample and the corresponding zUMI settings. LC-MS/MS proteomic data was uploaded to ProteomeXchange via the PRIDE database, with the project identifier PXD014512. Processed data can be found in Supplementary Table 3. MiRNA microarray data have been deposited in NCBI Gene Expression Omnibus (GEO) with the primary accession code GSE134827. Supplementary Table 6

1 summarizes processed miRNA data. nature research | reporting summary

Field-specific reporting Please select the one below that is the best fit for your research. If you are not sure, read the appropriate sections before making your selection. Life sciences Behavioural & social sciences Ecological, evolutionary & environmental sciences For a reference copy of the document with all sections, see nature.com/documents/nr-reporting-summary-flat.pdf

Life sciences study design All studies must disclose on these points even when the disclosure is negative. Sample size n=5 mice in RNA-seq and MS/MS experiments. sample size of 5 was chosen to allow power for non-parametric statistical tests (e.g Kruskal- Wallis), especially given the noise of the methods and the inter-mouse variability. m=3 mice in miRNA microarray. Here, the internal control embedded in microarray mothod helps with inter-mouse variability and allowed us to use 3 mice.

Data exclusions two populations (out of 40) were excluded from RNA-seq, due to insufficient number of reads. Number of reads threshold was set a-priori, in line with sequencing depth limitations. Stated in the Methods section.

Replication We have used 3-5 biological replicate for each experiment - all attempts at replication were successful as there was no sample which was excluded duo to outliers.

Randomization No allocation for experimental groups in our study. All five mice underwent same procedure.

Blinding N/A - all mice were treated the same.

Reporting for specific materials, systems and methods We require information from authors about some types of materials, experimental systems and methods used in many studies. Here, indicate whether each material, system or method listed is relevant to your study. If you are not sure if a list item applies to your research, read the appropriate section before selecting a response. Materials & experimental systems Methods n/a Involved in the study n/a Involved in the study Antibodies ChIP-seq Eukaryotic cell lines Flow cytometry Palaeontology MRI-based neuroimaging Animals and other organisms Human research participants Clinical data

Antibodies Antibodies used Immune-fluorescence antibodies: Alexa Fluor 647 rat anti-mouse CD73 (BD, cat: 561543, lot: 7128541, clone: TY/23, dilution: 1:50), Alexa Fluor 555 mouse anti-Ecadherin (BD, cat: 560064, lot: 6279687, clone: 36/Ecadherin, dilution: 1:50), Aldolase b (Thermo-Fisher, cat: PA5-30218, lot: UD2748636B, polyclonal, dilution: 1:50), Glutamine Synthetase (Thermo-Fisher, cat: MA5-27749, lot: UD2749352F, clone:GT1055, dilution: 1:200) , Goat anti-Rabbit IgG (H+L) Cross-Adsorbed Secondary Antibody conjugated to Cy5 (Thermo-Fisher, cat: A10523, dilution: 1:500) Goat anti-Mouse IgG (H+L) Cross-Adsorbed Secondary Antibody conjugated to Cy3 (Thermo-Fisher, cat: A10521, dilution: 1:200) HNf4a antibody (R&D, cat: PPH1415-00, lot: A-2, dilution: 1:350), Donkey anti-Mouse IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, conjugated to Alexa Fluor 594 (Thermo-

Fisher, cat: A-21203, Ref: A21203, dilution: 1:700). October 2018

FACS antibodies:

PE-anti-E-cadherin (BioLegend, cat: 147304, lot: B238754, clone: DECMA-1, dilution: 1:300) APC-anti-CD73 (BioLegend, cat: 127210 lot: B265946, clone: TY/11.8, dilution: 1:300) PE-Cy7-anti-CD31 (BioLegend, cat: 102418, lot: B212262, clone: 390, dilution: 1:300) APC-Cy7-anti-CD45 (BioLegend, cat: 103116, lot: B257634, clone: 30-F11, dilution: 1:300)

2 Alexa Fluor 647 rat anti-mouse CD73: validated in https://doi.org/10.1016/j.cell.2018.08.063, antibody registry: AB_11218786 Validation nature research | reporting summary Alexa Fluor 555 mouse anti-Ecadherin: validated in previous refs, reported in manufacturer's page: http:// www.bdbiosciences.com/eu/applications/research/stem-cell-research/cancer-research/human/alexa-fluor-555-mouse-anti-e- cadherin-36e-cadherin/p/560064 Aldolase b: validated in DOI: 10.1016/j.cmet.2018.04.003 Glutamine Synthetase: validated in the supplier's page for the same animal (mouse) and on the same method (IF): https:// www.thermofisher.com/antibody/product/Glutamine-Synthetase-Antibody-clone-GT1055-Monoclonal/MA5-27749 HNF4A: validated in DOI: 10.1016/j.jhep.2019.02.003 All FACS antibodies were validated using FMO experiments.

Animals and other organisms Policy information about studies involving animals; ARRIVE guidelines recommended for reporting animal research Laboratory animals C57BL/6JOlaHsd Three-months old male mice, obtained from Envigo laboratories (Israel)

Wild animals the study did not involve wild animals.

Field-collected samples the study did not involve field collected samples

Ethics oversight Mouse experiments were approved by the Institutional Animal Care and Use Committee of the Weizmann Institute of Science and performed in accordance with institutional guidelines. Note that full information on the approval of the study protocol must also be provided in the manuscript.

Flow Cytometry Plots Confirm that: The axis labels state the marker and fluorochrome used (e.g. CD4-FITC). The axis scales are clearly visible. Include numbers along axes only for bottom left plot of group (a 'group' is an analysis of identical markers). All plots are contour plots with outliers or pseudocolor plots. A numerical value for number of cells or percentage (with statistics) is provided.

Methodology Sample preparation Liver Perfusions and hepatocytes dissociation Five mice were anaesthetized and livers were perfused as previously previously described, with a few adjustments. A 27G syringe, connected to the perfusion line and pump, was inserted into the vena cava. 25ml of pre-warmed to 37oC EGTA buffer followed by 25ml of pre-warmed to 37oC EBS buffer with 2.3U of Liberase Blendzyme 3 recombinant collagenase (Roche Diagnostics) were cannulated into the vena cava. Shortly after the beginning of the perfusion, the portal vein was cut to allow drainage of the blood. After perfusion, livers were explanted into a Petri dish with 25ml of pre-warmed EBS and gently minced using forceps. Dissociated liver cells were collected and filtered through a 100um cell strainer. Cells were spun down at 30rcf for 3 min at 4oC to get hepatocytes enriched pellet. Pellet was resuspended in 25ul cold EBS. Cells Staining To discard dead hepatocytes, 22.5ml Percoll (Sigma) mixed with 2.5ml 10x PBS was added to the cells. Cells were centrifuged at 600rpm for 10 minutes. Supernatant containing the dead cells was aspirated and cells were resuspended in pre-warmed Hoechst buffer (DMEM + 10% FBS + 10mM Hepes). After counting, concentration was adjusted to 2x106 cells in 1ml. To determine ploidy of hepatocytes, DNA was stained with Hoeschst (15ug/ml). Resperine (5uM) was also supplemented to the cells to prevent Hoechst expulsion from the cells. Cells were incubated 30min at 37oC. Hepatocytes were centrifuged for 5min in 1000rpm at 4oC and supernatant was discarded. Next, cells were stained with Alexa fluor 488 Zombie green (BioLegend) to later enable the detection of viable cells by FACS. Cells were resuspended in cold PBS in a concentration of 106 cells in 100ul. Zombie-green was added in a dilution of 1:500. Cells were kept in a rotator in the dark at room temperature for 15min. After spinning down (1000rpm, 5min, 4oC), cells were resuspended in FACS buffer (2mM EDTA pH 8 and 0.5% BSA in 1xPBS), in a concentration of 106 cells in 100ul. Cells were stained with PE-anti-E-cadherin (BioLegend, cat: 147304), APC-anti-CD73 (BioLegend, cat: 127210), PE-Cy7-anti-CD31 (BioLegend, cat: 102418) and APC-Cy7-anti-CD45 (BioLegend, cat: 103116), in a dilution of 1:300. FcX blocking solution (BioLegend) was added in a dilution of 1:50. October 2018 Instrument SORP-FACSAriaII sorter (BD)

Software BD FACSDiva™ Software | BD Biosciences-US

Cell population abundance Abundances of sorted populations were 2%-6% from the total recorded events. Purity of the sorted populations was validated computationally by comparing RNA-seq data of the sorted populations with positive and negative controls.

Gating strategy Cells were sorted by SORP-FACSAriaII sorter (BD) using a 130 μm nozzle and 1.5 natural density (ND) filter. Lasers compensation

3 Gating strategy was corrected manually. In order to collect eight populations, each enriched with spatially-stratified hepatocytes with equal

viability and ploidy levels, events were screened through the following five nested gates (Fig. 3a-b): (1) hepatocytes gate from all nature research | reporting summary events – set by plotting FSC-A against SSC-A and excluding large clusters and small debris; (2) singlets FSC – set by excluding the margins of FSC-A and FSC-W plot; (3) singlets SSC – excluding upper margins of SSC-W when plotted against SSC-A; (4) live cells gates according to the Zombie-488 negative cells, comparable to unstained cells; (5) hepatocytes only, by depleting CD31 and CD45 (markers of NPCs), and (6) tetraploid hepatocytes, inferred by Hoechst histogram (Fig. 3a-b, Supplementary Fig. 1b-c). Hepatocyte size and overall protein content scale with ploidy, thus creating spurious correlations between the zonated surface markers (Supplementary Fig. 1). Sorting without ploidy stratification would result in inclusion of hepatocytes from different lobule layers, reducing spatial accuracy (Supplementary Fig. 1). We then plotted PE-intensity for E-cadherin staining and APC-intensity for CD73 staining. The positively stained cells were determined by measuring the intensities for unstained cells. The highest intensity for unstained cells was the threshold for the positively stained cells. Each population, CD73 positive and E-cadherin positive, was further gated to four equal subpopulations, representing graded intensities of the marker. Thus, subpopulations 1, 2, 3 and 4 had equal amount of events, 1 had the highest APC-CD73 intensity while 2, 3, 4 had gradually decreasing intensities of APC. Likewise, subpopulations 5, 6, 7 and 8 were equally distributed, 8 having the highest PE-E-cadherin intensity while 7,6,5 had gradually decreasing PE intensities. Populations 4 and 5 contained cells from below positive intensity threshold, to accurately resemble mid lobule hepatocytes, in which both CD73 and E-cadherin abundances are very low (Fig. 2). All gates were set for each of the five experiments independently, with a large overlap. Tick this box to confirm that a figure exemplifying the gating strategy is provided in the Supplementary Information. October 2018

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