Rats and axolotls share a common molecular signature after spinal cord injury enriched in collagen-1
Athanasios Didangelos1, Katalin Bartus1, Jure Tica1, Michele Puglia2, Bernd Roschitzki2, Elizabeth J. Bradbury1
1Wolfson CARD King’s College London, United Kingdom. 2Centre for functional Genomics, ETH Zurich, Switzerland.
Running title: spinal cord injury in rats and axolotls
Correspondence: A Didangelos: [email protected]
SUPPLEMENTAL FIGURES & LEGENDS
Supplemental Fig. 1: Rat 7 days microarray differentially regulated transcripts. A-B: Protein-protein interaction networks of upregulated (A) and downregulated (B) transcripts identified by microarray gene expression profiling of rat SCI (4 sham versus 4 injured spinal cord samples) 7 days post-injury. Microarray expression data and experimental information is publicly available online (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE45006) and is also summarised in Supplemental Table 1. Protein-protein interaction networks were performed in StringDB using the full range of protein interaction scores (0.15 – 0.99) to capture maximum evidence of proteins’ interactions. Networks were then further analysed for betweeness centrality and gene ontology (GO) annotations (BinGO) in Cytoscape. Node colour indicates betweeness centrality while edge colour and thickness indicate interaction score based on predicted functional links between nodes (green: low values; red: high values). C-D: The top 10 upregulated (C) or downregulated (D) transcripts sorted by betweeness centrality score in protein-protein interaction networks shown in A & B. E-F: Biological process GO analysis was performed on networks of upregulated and downregulated genes using BinGO in Cytoscape. Graphs indicate the 20 most significant GO categories and the number of genes in each category. G: MSigDB-Transfac was used to identify potential transcription factor binding sites in differentially regulated genes. The ten transcription factors that might regulate the highest number of upregulated (black) or downregulated (grey) genes are shown. The ubiquitous transcription factor SP1 is predicted to have binding sites for the greatest number of differentially regulated genes. H: The transcription factors MAZ, SP1, JUN and NFATC1 which are predicted to regulate a large number of differentially regulated genes (G) are significantly increased 7 days post-SCI in the rat microarray dataset. Graph displays their adjusted p value (T-Test) and fold-change upregulation after rat SCI (see Supplemental Table 1).
Supplemental Fig. 2: Axolotl 7 days microarray differentially regulated transcripts. A-B: Protein-protein interaction networks of upregulated (A) and downregulated (B) transcripts identified by microarray gene expression profiling of axolotl SCI (3 sham versus 3 injured spinal cord sample replicates; each replicate is a pool of 10 axolotl spinal cords) 7 days post-injury. Microarray expression data and experimental information is publicly available online (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE71934) and is also summarised in Supplemental Table 2. Protein-protein interaction networks were performed using StringDB using the full range of protein interaction scores (0.15 – 0.99). Networks were then further analysed for betweeness centrality and gene ontology annotations (BinGO) in Cytoscape. Node colour indicates betweeness centrality while edge colour indicates interaction score based on the predicted functional links between nodes (green: low values; red: high values). C-D: The top 10 upregulated (C) or downregulated (D) transcripts sorted by their betweeness centrality score in protein-protein interaction networks shown in A & B. Note that 4 of the most central downregulated (D) transcripts after axolotl SCI namely TSPO, ELAVL1, MYC (cMYC) and ISG15 are 4 of the most central upregulated transcripts after rat SCI (see Supplemental Fig. 1D). E-F: Biological process GO analysis was performed on the networks of upregulated and downregulated genes using BinGO in Cytoscape. Graphs indicate the 20 most significant GO categories and the number of genes in each category. G: MSigDB-Transfac was used to identify potential transcription factor binding sites in differentially regulated genes. The ten transcription factors that might regulate the highest number of upregulated (black) or downregulated (grey) genes are shown. Note SP1 is again likely regulating the highest number of differentially regulated genes but unlike rats (see Supplemental Fig. 1H) none of the transcription factors identified was differentially regulated in the axolotl gene expression array.
Supplemental Fig. 3: Visualization of intersecting rat and axolotl transcripts and gene ontology (GO) analysis. The 4 different groups of shared differentially regulated genes found in rat and axolotl microarrays 7 days post-SCI are visualised as protein-protein interaction networks made in StringDB v10 and CytoScape. Overrepresented biological process GO terms in each group and number of genes in each GO term are depicted in graphs. GO terms were retrieved using BinGO in CytoScape. A: Group 1; 153 genes upregulated in axolotls but downregulated in rats. B: Group 2; 156 genes upregulated in both axolotls and rats. C: Group 3; 77 genes downregulated in axolotls but upregulated in rats. D: Group 4; 228 genes downregulated both in axolotls and rats. Smaller networks (pointed by arrows) depict the genes that make up the indicated GO terms. Zoom-in to browse genes. Note that Group 1 (A) returned only 2 terms.
Supplemental Fig. 4: Comparison of rat proteomics and transcriptomics. A-B: Comparison of shot-gun high-throughput proteomics and microarray transcriptomics in rats identifies 110 and 90 molecules that were upregulated (A) or downregulated (B) both at the mRNA and protein levels 7 days post-SCI. C-D: The 10 most significant biological process GO terms retrieved using BinGO in the 110 upregulated (C) and 90 downregulated (D) proteins. Note that “extracellular matrix” and “collagen” categories are the most significant GO terms in the group of 110 upregulated proteins after SCI (C). Proteomics identifications and protein spectral counts for each sample can be browsed in Supplementary Tables 3 & 4.
Supplemental Fig. 5: Type I collagen staining in advanced 12 week-old lesions. A-B: Collagen-1 (COL1A red; the antibody recognises both COL1A1 and COL1A2 chains) and CD34 (green) were costained in 30µm thick T10 injured spinal cord cryosections. Spinal cord tissue was collected 12 weeks post-SCI. (B) is a magnified area from (A). C-D: COL1A (red) was costained in 30µm intact T10 spinal cord cryosections with CD34 (green). (D) is a magnified area from (C).
Supplemental Fig. 6: CD34+ cells are distinct from CD45+ cells in lesions 2 weeks post-SCI. A-B: CD45 (red) and CD34 (green) were costained in 30µm T10 injured spinal cord cryosections. Spinal cord tissue was collected 2 weeks post-SCI. (B) is a magnified area from (A). CD34 and CD45 are proximal but there is no cellular colocalisation. CD45 (pan leukocyte marker) will likely stain leukocytes including monocytes. The marker is retained in macrophages and is also expressed by activated microglia (albeit less than infiltrating monocytes and tissue macrophages). CD45 staining pattern resembles activated macrophages and microglia. C-D: CD45 (red) was costained in 30µm intact T10 spinal cord cryosections with CD34 (green). (D) is a magnified area from (C).
Supplemental Fig. 7: PDGFRB mRNA is upregulated after SCI. TagMan qPCR for PDGFRB of intact and injured spinal cord segments 2 weeks post-SCI. *** p≥0.001 T-Test; 6 intact vs 6 injured spinal cords. Data is mean +SD.
Supplementary Figure 1
UPregulated Genes RAT 7D UPregulated Genes BIOLOGICAL PROCESS
A GOLM1 SERF2 LIMD2 SLFN13 KLHL6 LYRM5 MFSD11 TMEM181 ARMC10 BRI3 CR1L TMEM206 NHLRC3 SIDT2 CCDC115 FAM76A FAM219B GUCD1 SLC25A45TMEM39B ESYT1 TMEM168 OGFOD3 NTMT1 SPATS2L FRMD4B SMPDL3A FOLR2 OAF PLEKHA4 NT5DC2 KLHL5 POC1B SOGA1 S100A3 FILIP1L C5orf43 CCDC125 TMEM208 NKAIN1 FAM198B ZMYM5 HRCT1 C E
INMT RARRES1 MXRA8 PTPLAD2 PSCA SFT2D1 MFSD12 ALPK3 FAM193A ZFAND3 MPV17L TMEM37 GINM1 SCAMP4 PLAC9 FAM108C1 FKBP15 VGF COA4 IAH1 ABRACL TMEM131 NT5DC1 PARP12 TMEM140 APOOL SLAMF9 GSDMD CEP128 ZDHHC6 SLFN5 RPP25L FAM105A FAM76B TMEM123 GPR84 ZDHHC7 EMP3 FEZ2 ATP8B2 CHADL LRRC8B GPR34
ZNFX1 IER5 EMP1 SLC35A4 CALHM2 ATP10D ADAP2 SEPN1 PSMG2 OSBPL11 CCDC93 MTPAP LRRC40 ABHD2 SCAND1 PION TOR4A LEPROT LRRC8D ZFP36L2 RNF169 SCPEP1 LMAN2 C20orf111 REXO2 Sep-09 OMA1 CRYM PLGRKT CDCA3 LRP10 DNAJC13 LRRC41 RAB20 OTUD1 RNF217 TTPAL ISLR ALDH2 ZCCHC6 ARL4A DNASE1L1 KCNN4
SWAP70 WSB1 TFPT RNF122 SLC12A9 TRAFD1 STK19 PAPD4 SLC25A24 SBF2 NPEPL1 NLN IRGM PTTG1IP TBC1D23 TBC1D2B CDK2AP2 HILPDA TMEM14C PDCD2 XYLT2 UBTD1 EPB41L2 OST4 CRIP1 TM9SF1 KCTD12 NAV1 HMGN2 PPFIBP1 EXTL3 TATDN1 SULF2 FCRL2 CLEC12A GNPTAB TIMM22 MS4A6A LRRC59 TNFAIP8L2 QSOX1 EIF2D HLX
LILRB4 F8 SMIM3 WDR83OS MYO7A PRRC1 KDELC2 JTB PTPLA ARL11 NCLN PGAP2 EBPL DSCR3 SERTAD2 ADAMTS9 CENPW METRNL CCZ1B MTX1 SLC35E3 FBXO6 SLC25A39 DLGAP4 ZNRF2 TFEC NPL RENBP RTP4 IFI44 PHLDA1 SLC15A3 SLC15A4 CYP20A1 DDAH2 TEX264 ILDR2 RNF213 TEX261 SLC10A3 SLC35B1 LMF2 LAMA4 Most central Genes
NUDT4 SASH3 DCAF11 RELL1 COX16 VPS13C FAM107B DHRSX DENND6A DENND3 TMEM248 CD276 WDR81 MPV17L2 CLIC1 FNDC3B ACOT1 PRSS23 RNF149 PDK3 FBXO46 BCKDK RNLS PCED1B TMEM86A RCBTB2 TMEM176A ATL3 BTG3 ETFDH FAM110A APBA3 TTC7A SPSB1 SYNGR1 ARHGAP42 LRRC42 CGGBP1 EVA1B ACOT9 C2orf18 CPNE8 BZW2 cellular process TTC13 EML3 CTHRC1 ANKRD49 NXPE4 SOWAHC EPSTI1 FBXL6 DRAM1 LMCD1 TMEM150ATMEM223 PXDC1 LYSMD3 RCN3 FABP5 DNAJC14 FAM49B SBNO2 SLC38A10 EEPD1 SP140 TMEM176B SZRD1 MOSPD3 VNN1 KCNE4 FRMD8 KANK2 RAI14 FAM111A OLFML3 CAPN5 CCDC90A ZFYVE26 RDH10 MFSD5 MYADM TMEM134 SLC44A2 CD300A AVPI1 LHFPL2 response to stress CDKN2AIPNL RP9 FADS3 FAM46A MFSD1 RNF138 GPSM3 IRF2BPL CAPRIN1 CYBASC3 TSC22D4 SPPL2A TNFAIP8L3 EXO5 VASH1 FGGY UAP1L1 YIPF1 DESI2 KRCC1 MIDN ZFX LYRM2 PQLC3 SLC2A5 MKLN1 GLTP MTMR12 ELK3 STAB1 ZBTB8OS OGFRL1 FIBP FUBP1 RRAGC SLC28A2 SLC29A3 TRIM5 TRIM34 SLC35B3 NIPA2 MIF4GD FKBP10 TSPO FAM48A UBE2G2 SPTLC2 RYK TMEM209 SRD5A3 RAB27A MREG HHEX ALDH16A1 LPCAT3 HELB TMEM48 RFT1 SLC31A2 NAAA TMED3 NFAM1 UXS1 FUCA1 NUSAP1 STK10 CCDC90B ELK4 PXDN SRBD1 HTRA3 PDLIM4 MT1A IER5L AMMECR1L MEMO1 DNPEP SGCE RAP2B POLG UBL4A PRR13 MPST PIGT USP38 FGL2 STK17B immune system process
HN1 SYNPO ATAD2 COMMD2 CCDC22 CTSH PEPD PPIL1 ARRDC1 ZDHHC14 TMEM43 SH2B3 TRIB1 TTK NINJ1 CUEDC2 CDK12 ATRX MEX3C ABHD12 SGPL1 LTBR FXYD5 MPLKIP WDR26 RBCK1 APIP CD37 SNX8 AKAP10 PIGX CYB561D2 NPRL2 IWS1 MSL3 GAPVD1 PLXNB2 ZDHHC13 DPP7 SH3GLB1 CCPG1 PRCP ICOSLG
MRPL9 KIF22 TNFSF4 PRKD3 SLC4A7 SEC14L1 OSTF1 PLEKHF2 LGALS9 CAPG POR ISY1 Sep-10 CLEC10A RAB32 RNH1 SNX12 RAB31 NXT1 AFF1 SH2B2 SLC8A1 GCN1L1 MPEG1 ACBD3 FLOT1 ARRDC4 EAF1 CHD1L XYLB FUBP3 TAPBP TIFA ILVBL TM4SF1 CD53 SNX18 ANO6 RNF114 MOB3A SLC12A4 IER3 AGTRAP TP53 response to wounding
SLC38A7 TSPAN9 PTPN7 LACTB TIFAB TCF19 SLC35B2 ERLIN1 RCN1 TMEM179B UBE2F VAT1 C17orf61 FCGR1A CAMK1 ST14 TNFAIP6 SPINT2 BCL7C MTHFS RBM47 ZDHHC16 COMMD4 EHBP1L1 ZDHHC4 SS18 PLEKHA1 PELO PLEKHM3 TMEM165 CPNE3 SLC35A3 HEATR5A PI16 TOR1B SH3BGRL3 RBMS2 KTI12 MATN2 ZBTB34 HMBS ATP13A1 DENND2C SEMA3D positive regulation of biological process CCDC43 SLCO2B1 TSPAN31 FNBP4 SLC44A1 RAB5C FKBP14 TAMM41 PRELID1 N4BP2L2 POMT1 LAPTM5 GLT8D1 SH3TC1 TAP1 SSBP1 MAPK1IP1L DUS1L HOMER3 RNFT1 AASDHPPT SSH2 MOSPD2 MICAL1 TYW1 DUSP11 CNIH4 TLK2 KXD1 CNPPD1 RASGEF1B HAUS1 SLC22A18 SHISA5 RIN2 VPS54 MYCL1 CTSE HS2ST1 SSH3 RAB34 PREP COPS3 ELAVL1 TRIM27 PROCR SYNGR2 CYBRD1 FNIP2 KLF3 AGFG1 SP110 CHURC1 TRIM47 NIPSNAP3B SLC7A7 BMP2K ARFIP1 DNAJC1 FAM46C COTL1 TBC1D15 PLXNC1 ERP29 EVI2B RCSD1 C11orf10 NPC2 DRAM2 TMEM87A ARF4 ACP2 CTSC AIF1 MRC1 ALG8 XBP1 SOCS6 CLN6 OLR1 XPNPEP1 GPNMB RSAD2 CP UFM1 SNX7 LYL1 response to chemical stimulus
MYLIP CNPY2 IGF2R UBL7 TOM1 PLBD1 BIN2 UBN1 GLIPR1 TUBB6 SHC4 FXYD2 NADK TMEM214 KATNA1 ADPRM MASP1 SH3D19 SMC6 DGUOK NASP SLC39A6 VKORC1 SCARB2 POP4 RPP40 FERMT3 NAMPT CDC42SE1 HYAL2 GTF2H4 TAGLN MARCKS ALDH18A1 CMTM6 MAN2B1 AXL ZFAND6 RARRES2 CMKLR1 H2AFJ CDK20 SHCBP1
DDX47 SOAT1 CH25H GAMT NFIL3 TTC28 CD68 ERF PPIH GALNT2 EPB41 MRPL23 RGL2 TMOD3 DAP CD33 SRA1 RNASET2 NIT2 FAM3C PTCD3 NMT1 EHD2 TAGLN2 ENTPD2 ST6GAL1 SRXN1 UCP2 ST3GAL5 LYVE1 PMP22 SAT1 QPRT LPAR6 MBOAT1 NAT1 CTBS EIF4EBP3 ADAMTS5 PI4KB KLF6 IPO5 ARHGAP30 AKT1 signal transduction SCYL1 IL33 MFAP3 ACD SIPA1 TEAD1 PLIN2 UXT TNFSF13 MYOF NEK6 PABPC4 CMTM7 MDFIC LGMN RBM3 TXNDC12 AP1S2 TXNDC5 MYO1F TXLNA BLOC1S6 SERP1 KDELR2 ELF1 PLIN3 RCAN1 TAOK3 KDELR3 SSNA1 MKNK2 CENPB IL17RA LIMD1 HSD3B7 CD48 CORO1A SLC35C1 SLC6A6 DAPK3 DSC2 ME2 EDEM1 cellular component organization BIN3 LAMP2 VPS18 CELF2 RNASEH2B FCHO2 MTHFR KLF11 ESM1 ARHGAP27 CCS MPZL1 TNFAIP2 LITAF TNS3 CUX1 TRPV2 CYB5R4 LSP1 HCST SLC50A1 STEAP4 ANTXR2 EML4 EDEM2 STOM PIEZO1 P2RX4 LIPA FARSA RGS16 SLC12A7 GCH1 FHL3 CORO7 APOBEC1 AP3B1 CLEC4A RIN3 GABARAP MYO1E NECAP2 SDF4 SRC FAM20C LOXL2 RNF128 BTG1 FSTL1 TRAF7 BNIP1 OSGEP PNRC2 GTPBP10 MAZ SLC30A7 WDFY1 MANF INF2 TFPI2 TRMT6 BST2 ASGR2 NUCB2 HIST2H2BEADIPOR1 CKLF CMTM3 PAOX FAM129B ADAMTS1 SERPINF1 FOXP1 ANXA4 KIF20B GLS AGA ORAI1 XRN2 CLCN7 SLC39A8 OSBPL8 MANBA CHD7 RAB8B PDLIM2 C6orf108 response to organic substance EEF2K PDPN LGALS8 PMP2 RREB1 CRLF2 ABI3 DUSP6 SURF4 EIF1AD TCN2 SLC39A11 SLX1B LCP1 HPS1 HTATIP2 PDZD11 TARS SYNCRIP CSF3R FDX1 CLEC7A ABCC3 MCAM SLC31A1 COMMD7 OSTC BCOR CARS SERPINH1 KCTD10 CPSF4 NUDT21 LPXN GALC LAMTOR5 LAMTOR3 PPIB PCCB UMPS DPYSL4 LDHA PSMB9 HMHA1 PDIA4 PRPF3 GRK6 IFI35 GSTO1 ADA CFH SH3PXD2B MAN1C1 WASH6P CCDC53 CERS6 CERK COL3A1 IFITM1 GPX7 ACSL5 GABPA AFAP1L2 UTP14A NRF1 MCRS1 HEXA HBP1 MAML2 TUBB4A FBLN2 CASP4 THBD CNDP2 CNDP1 NNT IDH2 RBKS RPIA PDLIM7 FLNA COL12A1 IFI27 DAGLB CPT1A PTAFR JUN macromolecule metabolic process ANXA7 SRI MGLL GBP2 CSNK2A2 ZEB2 HNRNPAB SOX4 ENPP3 DHX58 CERS5 HK2 ANGPTL4 EXT2 TRH GPX8 ERP44 PRDX4 OCLN AHCY AHNAK NAGA CD99 CSPG4 SCAMP2 PDCD6 ERAP1 ARAP1 IFITM3 MMP19 FILIP1 GMFG SDF2L1 SEPHS1 SCLY GM2A PTPRO MOGS COL6A3 NUBP1 CTSA GTF3A NUBP2 multi-organism process COL5A2 COPZ1 PNLIP DOCK11 SRGAP2 CALD1 AP2S1 ARHGAP25 KDM2B ADM COL6A1 DCP1B CAST PLA2G15 PTPN18 FLI1 RCL1 CD83 FKBP5 CHST2 CD63 ARHGAP22 RAB14 RUFY1 PVR DYNLT1ARHGAP11A PTK7 RBM5 N4BP2 DCTPP1 DDX21 BET1L SEC22A S100A6 DDX60 HMGCL CASR MGP TES CHSY1 CORO1C IFI30 CHST12 DCXR CFD MGAT4B FBXO18 DPM2 CLN3 ANPEP AKR1B1 PLOD3 APH1A KLF10 COL11A1 PTPN6 SPG21 RBMS1 RRBP1 TDG RASA3 GMPPA CANT1 NAGLU CENPL DOCK6 POFUT2 CFP H1F0 KDM6B SLC30A1 SLC39A1 NT5C2 TIAL1 MGST2 IDUA PYGL PAK1IP1 SNAPC3 DDX18 PARP14 COL9A3 ZMIZ1 CARHSP1 STYX MYC metabolic process THBS4 LOXL1 NAGK CTSK RFX1 POSTN PLD4 LPCAT1 GNPDA1 SVIL TALDO1 B3GALNT1 FGD2 ARHGAP18SLC35A1 ST3GAL4 CNKSR3 PLD3 REN CTSZ FAM64A HIP1 GNS TAGAP LIMA1 CSTB LYPLA1 KDELR1 HTR2B GPS2 P2RY6 SND1 SLC16A7 EMB HMGXB4 RNF144B DTX4 RGS10 PLOD1 PCOLCE P2RY2 C5AR1 CX3CR1 GAS7 TLE3 WHSC1L1 IFITM2 FAM96A FUT4 B3GNT2 NES GLT25D1 TXNDC17 C3AR1 TCEB3 PTGR1 MAPKAPK2 VAMP5 CLTA AMOTL1 HEBP1 CCNG2 GLO1 AK2 CTSL1 CRYZ ABCB4 P2RY12 NID2 NT5C NID1 LAMC1 PA2G4 STXBP2 SNX6 C1S IFIT2 PARP2 IL6R ENTPD1 NT5E CHL1 RPS6KA3 ANXA11 ANXA3 VCAN ISG15 primary metabolic process H2AFY TMED9 NFYA PTGFRN ACAA2 HADH DDX54 BCL2A1 TREM2 DNAJC3 FAM125A BUB3 MAP3K8 VPS37B ALG5 MX1 ATF1 ZNRD1 RRAS2 RPS6KA4 MLX TOR1AIP1 CD9 MXD4 RRM1 DNASE2 PGD PGLS ACTN1 FN1 MPI PMM2 LOX EFEMP2 AEBP2 ACTA2 OPHN1 SEMA3C HMGA1 SDCBP ADAM9 ARAF PLEKHO1 immune response CLIP1 TOR1A TOR1AIP2 IFIT3 MAD2L2 ARHGAP9 SUMF1 ARSB CHMP1B MMS19 TNFSF12TNFRSF12A PDE3B RGL1 CDYL ARHGAP24 LUM NCKAP1L SNX9 ETF1 ARHGAP17 GNA15 MAFB CYFIP1 WHSC1 GBA PSAP FCGRT RHOBTB1 CYBB PFN1 DNAJB11 TBC1D1 RAB8A CAP1 RHOJ PTPRJ RBPJ MYL12A STARD13 PRKAB1 IFNGR2 LASP1 EIF2A TEP1 IL18BP ELMO2 PARP4 PLCD1 TGM2 NUP155 PLTP SCARB1 MSN ANXA1 S100A11 NUP205 CASP2 ADAM15 TOPBP1 USF2 TRIO PLAU DYRK2 FCGR2B IRF5 GDA XDH PDE7A TNR BHLHE40 ADCY4 PTGS1 PLA2G4A PPP6R1 MAPKAPK3 DAB2 PNP DGAT2 DGAT1 NBN ASAH1 CARD14 PNKP BTK CD8A positive regulation of cellular process GPX1 GSS TAX1BP3 DSCC1 MGAT2 MAN2A1 ITGB5 WLS WNT4 DTYMK TK1 GLB1 GUSB TGFB1I1 COL16A1 SDC1 SH3GL1 EGR2 NFATC1 CYP1B1 COMT CALU MX2 LTC4S CIB1 FCGR3A CD86 CENPF PRKCDBP PTBP3 LTA4H CXCL10 PF4 MT2A DOCK8 KRI1 AATF RGS2 MAK16 COL1A1 RALB CCDC86 SLC30A5
MVP IGFBP7 PBK RAB13 TPP1 CLN5 ZFP36L1 HAT1 ACP5 HES1 PSMB8 SAR1A NFASC SLK GEM ZWILCH COL5A1 WDR1 TBXAS1 HEXB CSF2RA ELAVL1 CDK5RAP2 MAN1A1 LGALS1 MGAT1 THBS2 PIK3AP1 S1PR3 CTSB CTSD CHFR COL5A3 TNC NCAN TSPO MAP3K3 GGCX F10 ABCG1 PSME4 ST3GAL1 GCNT1 signaling ALOX5AP BMP1 GRN SLPI PPIL3 GIPC1 PGM2 DERA MAP2K3 ADAM17 HBEGF ARHGAP15 PTRH2 GPX3 NMI DCTD CITED2 FABP4 MYO1C RAB3IL1 TRPC6 MERTK GLRX FBN1 PROS1 SPC24 GNGT2 STK3 SPC25 WDR5 POLR1D GNB1 ASH2L PDS5A RIPK3 POLR3H WAPAL SMARCD2 PSME2 USP18 ISG15 TCF7L2 SMC4 UBL4A signal transmission SMC2 ITGA6 MCM4 ANAPC11 JUNB PSME1 LY96 EIF2B1 POLR2D POLR2I CTTNBP2NL BLNK DDX58 TRIM25 IGF1 TRIP10 ARID1A GNG5 UHRF1BP1 DDX39A SAV1 UBE2C NUP160 S100A4 GMNN CCL4 NONO SFPQ DDX20 ITGB1 BID YEATS4 SRSF6 MMP14 EHD4 NFKBIB NAA38 EHD1 STAG1 LSM3 RARS PPP2R1B TICAM1 QARS IGFBP5 MBD2 CHMP2A MYC DBNL TIMP1 CBLB MAP4K1 PLD1 IRF7 SPP1 CD44 CCNG1 PTPN12 GINS4 AKT2 CD8A B2M CHRAC1 PIK3CD CNOT6 SF3A3 RHOC BNIP2 TLN1 RPS27L TLR2 SMURF1 SNRPA MRTO4 MKI67IP LGALS3BP LGALS3 BAZ1A HCLS1 ITGA1 PTPRC DIS3L LPL TP53I3 SPRY1 NCF4 signaling process GALM RCC2 PTBP1 NIP7 SSR1 SSR2 NDE1 GALK1 HNRNPUL1 CD4 HMOX1 APAF1 TMEM173 MKI67 SEC11A C1R TLR7 PLXNA1 APOE GADD45GSMARCAL1 NFE2L2 NRP1 STT3A PRC1 LSM10 CHD1 SSRP1 PPP1CA PPP1R15A COL4A1 COL4A2 VIM FZD1 MAFF CD14 BLM PPP4R1 PPP4C SKAP2 PPIE WIPF1 MRPL22
RBM10 FBL LBP KIF20A PYCARD MYH9 RBM39 SH3BP2 CAPZB SSR4 NHP2 HIST1H1C TGIF1 FCER1G NGFR STK38 CSDA RALGDS ETV3 PDCD11 NOC2L VAV2 ENG APRT INPPL1 H2AFZ NCBP2 PARP9 DTX3L UNC93B1 ABCA1 NR1H3 TPM1 TPM4 NCAPH2 RAE1 CDKN1C TACC3 HNRNPA3 GNG12 FHL2 MAFK COL1A2 response to biotic stimulus MMP7 CCL2 TNIP2 STRA6 RBP1 HEATR1 RAP1B SDC2 IRF8 ADRB2 TRIP6 POLD4 USP39 CDKN3 DAPP1 ARIH1 UBE2L6 TRAM1 ALG14 NUP88 MAF DPAGT1 PDIA6 P4HB RNASEL USP1 LMNA PTPN2 LRRFIP1 LMNB1 TOP2A MINA VPS26A SNX2 EIF4A2 TLR8 NABP1 INIP ANGPT2 NOD1 BCL3 TIE1 TCIRG1 response to other organism APEX1 ATF7IP ATP6V0E1 APBB1IP CEBPD IL10RB IL10RA ATP6V0A2 SEC24D LY86 MEF2A MYO9B MEF2C EIF4E2 SEC23B PELI1 TEC SNAP29 ARF6 PLK2 MDC1 TPM3 SERPING1 SNRPF IFNAR1 RPA3 SNRPB PAK2 RPA2 STAT2 CDC42 CSK IRF9 JUN ATF3 RPL11 RPS5 MED29 MED8 ARRB2 MDM2 NCSTN PSEN1
SMAD2 SMAD3 BIRC2 DIABLO RPL14 RPL18 RPL18A RPL12 PXN GIT2 BCL10 CARD11 ETS1 C1QA C1QC NCK1 FEN1 TMED10 TMED2 DNMT1 RPL22 PRKCQ PCGF6 RNF2 TNFAIP3 NRAS RAF1 UBA52 RPLP0 EED TNIP1 ARHGDIA GTF2H3 MAP3K11 EZH2 GTF2H1 AURKA TP53 KIAA0101 PCNA CASP8 TYK2 RPS15 0.000 0.010 0.020 0.030 0.040 0.050
TRADD CREBBP SP100 FKBP1A IRF3 SEC61A1 SEC61B PML UNG TGFB3 AKT1 ARHGAP1 TGFBR1 MED14 MED11 ARPC5 ARPC2 MAPRE1 AURKB TAF9 TAF6L HDAC1 SIN3B DCN TGFB1 RPL7 IMPDH2 GMPS CBL TNFRSF1A RAC2 MCM2 MCM7 SMARCE1 RCOR1 MED12 SP1 GTPBP4 NSA2 RFC3 RHOA C1QB PRKDC BAK1 SMN1 VAV1 LCP2 SYK ACTL6A RFC4 RFC5 ITGAX ITGB2 SIRPA CD47 CNN2 FSCN1 EEF1G EEF1D ANXA2 S100A10 STT3B ARHGDIB FOS RPN2 FYB SNAP23 VAMP8 SMAD4 TEN1 FOXO1 IRAK2 EIF3C MAGOH NUP37 SEC13 IL18 CASP1 TGFBR2 DDOST MCM6 MED13 GATAD2A USP3 EIF3D CNOT1 Betweeness Centrality 0 CNOT6L CTNNB1 CCND1 MYD88 TLR4 RIPK1 OBFC1 SRC STAT3 IFNGR1 STAT1 ARPC1B ARPC4 EEF1B2 MTA2 CCNB1 CDK1 ARPC3 ACTR2 NUP62 RBL1 GADD45A NUP54 CHMP6 VPS36 TFDP1 PKN1 ATP7A ATOX1 SF3B3 PHF5A SNRNP40 AXIN1 CCR5 CCL3 STK4 RASSF4 BCL2L11 MCL1 EIF3I EIF4A3 PRKCD SEC61G 120240360480600720840960 CDK4 IFNAR2 CDT1 HCK CAV1 AKAP13 EZR RRAS PARP1 SF3B5 EXOSC5 EXOSC8 HNRNPF IQGAP1 THOC6 ALYREF TAL1 LMO2 ZYX VASP CYBA IL1RAP LYN NCF1 MMP2 CASP3 IL1R1 TIMP2 EIF3L TYROBP NEDD4L SGK1 SNRPD2 FYN ITGAL CCNB2 ILK CSF1R PTPN1 PHC2 CXCL12 CXCR4 CKS1B 10801200 BAIAP2 INPP5D IRF1 PSMB10 ECT2 CEBPA CEBPB SHC1 ITGAM ICAM1 RELA CKS2 EIF2S1 EIF2AK2 PAN3 PABPC1 CCNA2 SRSF9 CBFB RUNX1 RACGAP1 Number of Genes
DOWNregulated Genes B RAT 7D DOWNregulated Genes D F BIOLOGICAL PROCESS EPM2AIP1 NECAB2 FAM5B CCDC149 PCDHB10 MPPED1 ARMCX1 SUGP2 TMX4 TMX2 C1QTNF4 HOXD8 CHST1 TMEM179 PPDPF CHST10 HUS1 KCTD4 MLLT11 EPDR1 SLC25A34 SKIDA1 BTBD8 PCP4L1 NCDN TSHZ3 ARMC9 C17orf79 TMEFF1 ZCCHC12 ZDBF2 RBM11 FBXO41 WDR37 EFR3A MOBP DACT3
TMEM150C ENHO FAM189B ATRNL1 KLHDC7A PLCXD2 MAL RBMS3 UFSP1 EMC9 ZC2HC1A MKRN1 SNX16 SVIP C8orf42 ZCCHC24 AAED1 RASGEF1A RPP25 GPRC5B BEND6 CCDC92 KLHL32 PRAF2 MOG TMEM106C IGIP FRMD5 ZFP91 LY6H EXTL2 PLEKHD1 CRISPLD2 ZFP106 ZNF23 FNDC5 NIPAL2
SCRN1 RAPGEFL1 TASP1 RNF112 PPP1R14C VWA8 ZMYM2 CDIP1 SFXN5 LRP11 LSAMP VWC2 RELL2 TSPAN33 LIX1 FAM184A BTBD3 NDUFAF7 TTC33 SNRK CYYR1 BTBD11 SLC25A25 FUT9 DARC MFSD6 FAM168B WDR47 TRIM36 TMEM38A FAM222A KLHL23 FAM84A TMEM41B TMEM35 SLC25A23 EFR3B TMCC2 THSD7A HGSNAT TRIM2 PLEKHB1 RNF180 ANKRD13D TET1 FN3KRP SUSD4 TMEM91 MBD5 FLYWCH1 RUSC2 FAM19A5 PHYHIP IGSF21 SEZ6L2 AIF1L TMEM62 ABHD8 FAM32A PIGY ROGDI SMIM5 SPTSSB FAM126B VSTM2L DCAF12 CXXC4 CREBL2 CHODL CREG2 GATSL2 CCDC81 RNF187 NOL4 Most central Genes transmission of nerve impulse CEP19 BEX1 FUNDC2 CCDC30 PHACTR3 NRSN2 FAM69B SLC35G2 SLC35F4 SHISA4 SH3BGR TENM3 NEXN LYNX1 NFIC UBN2 SALL2 CLSTN2 ZDHHC20 TLCD1 MIA3 CELSR2 TENM4 PRPS1 MANEAL ANKRD34A PDZD8 KCNJ14 PCSK1N CCDC28A OSBPL6 RUFY3 SEC14L2 TTC19 TAB3 N4BP1 ITFG1 LRRC49 FAM120B NR3C2 SLC6A15 PURG ZMAT3 NMT2 CHCHD10 FLYWCH2 CSDC2 SULT4A1 LUZP1 TENM2 CELF5 FSD1 ARHGEF26 NUDT10 TSPAN17 FAM101B FHOD3 TMEM132E SAMD14 DOCK5 PLCXD3 STRBP RNF157 NUDT3 SLC25A33 HERC1 SH2D5 CCDC126 NKIRAS1 FAM163B TMEM246 ABCB9 DNAJC21 FAM98A CDC42 synaptic transmission TSNAX B3GALT5 STAU2 BLOC1S5 SYNDIG1 CBLN1 DIXDC1 YAF2 REEP6 ST13 SACS COBLL1 TAGLN3 CAMTA1 GPRASP1 KCTD9 CYHR1 TCF20 RUNDC3B KRT10 CABLES2 ABHD3 DZIP1 ARL6IP4 TOX PITPNM2 SAMD12 ART3 CYGB TOM1L2 FBXO33 PAIP2B FSD1L FAM49B CD59 GIGYF2 ISOC1 nervous system development PRUNE2 NCOA7 GJB6 GLCCI1 GREM2 SCXA KAZN SLC43A2 CELF4 SV2A USP54 TRIM16 COQ3 ARHGEF9 CHIC1 ANO3 PCDH9 SYNGR3 ERMN YPEL3 YPEL5 FAM110B NDRG4 SCAPER RALGPS2 HAPLN1 NICN1 TSPAN7 AMIGO1 LURAP1L JPH3 CTXN2 ELFN2 CX3CL1 ATMIN COBL SVOP
UBXN2A FAM190B KBTBD3 TBC1D19 GLRX2 LAMP5 ALG2 PRMT8 SORL1 SLC6A17 CCDC117 CCDC141 HAPLN4 LRP3 PANK1 CBLN2 DISP2 CSRNP3 FAM43B SLC2A13 LANCL1 ADHFE1 GCA ZBTB7A MAGEE1 SLC25A27 CYB561 TPD52L1 ANKRD34B PANK4 CADPS2 ZSWIM5 MORN4 CRTAC1 MRAP2 NRSN1 ATPAF1 SNCA establishment of localization IRGQ NXPH1 ENDOD1 PANK3 AGTPBP1 ZSCAN18 ANKS1B NIPSNAP1 TM2D3 TMEM151A NEK7 ELMOD1 STARD10 PRR12 PLEKHH1 RNF182 TMEM50B SMS NELL2 HECW2 TSC22D3 HPCAL4 SLITRK3 STEAP2 PROSC TTLL7 P2RX6 LYSMD2 LYSMD4 NGRN PARP6 RPRD1A FAM123A FAM57B FYTTD1 PELI2 ZBTB11 transport FRY TRAPPC2 SHROOM2 HAPLN2 PCDH17 SLC24A3 MDGA2 SNX10 USP31 TPRKB NSG1 GKAP1 ZBTB1 HMP19 EXTL1 MRO ATP9A AJAP1 NINJ2 NKAIN3 REPS2 PSD3 SLC45A1 EID2 MAB21L2 RNF208 PRRT1 SLC6A9 DTD1 UBR3 DZIP3 FBXO21 MOK SLC4A10TMEM178B TDRKH CLUAP1 DLG4 ST8SIA3 FSTL5 CPNE6 KCTD17 IFITM10 RNF152 RNF165 CASKIN1 IQSEC1 PAQR6 PAQR7 SMYD2 NELF ARNT2 IQSEC3 NUS1 MTA3 DNM3 HPCA SUB1 RAB9B HOXD1 ACSL3 KCNK3 USP29 DGCR6 RIT2 CDR2 IGDCC4 PDZRN4 DAAM2 RABL6 CALY ASIC1 SLC7A14 NXPE3 BMPER localization SLC9A6 GDF11 SLC1A2 RTN2 TRAM1L1 HHATL NRIP2 ZYG11B SLC30A10 NRIP3 AKAP11 SGIP1 PSIP1 SLC13A3 ATP6V1G2 PAIP1 SLC4A3 USP35 KIAA0664 HACE1 TPM1 KLF12 ZDHHC17 CTNNBIP1 CACYBP ELAVL2 SLC39A10 CORO2A HBB SPOCK3 COA5 COX11 ZC3H6 RALGAPA1 CPSF6 MYOC OLFM3 WDTC1 neurotransmitter transport PDP2 PPTC7 B4GALNT1 EIF5A2 AHCYL1 PCDH19 NMRK1 FAM131B CLSTN3 FAM155A RNFT2 ACOT13 RHBDL3 C22orf25 CPEB1 TRO AFF2 ATL2 COL25A1 SLC30A9 SYNPR BCL7A CDADC1 ARL16 DTNB HERC3 KLHL15 TCEA2 NAP1L2 UBE2K UBE2O CHD6 WHSC1 ATP2B3 AAK1 MMP24 TIMP4 cell-cell signaling AP3B2 CRYZL1 EXPH5 IMPACT EIF1B MTUS2 LANCL2 VSTM2A NCAM2 ZFYVE9 AQP11 MAGI1 PPFIA3 KCNK1 FAM19A2 FAM171B NUDT11 EHBP1 FAM189A2 RBFOX1 PNMAL2 NTM ABCG4 VSNL1 SLC10A4 OSCP1 SLC25A18 ELAVL3 FA2H PCP4 DNAJC27 PURA ADARB1 PAQR8 GPR137 HAGH CCDC85C
SYT16 SLCO1C1 CCDC85B GARNL3 SLC24A4 ACOT7 DCUN1D4RAB11FIP3RAB11FIP4CAMSAP1 TRIM3 SLITRK1 SLC38A2 MTAP AIFM3 LIMCH1 TMEM33 DPCD GLS2 CHCHD6 PTPLAD1 NADKD1 PCMT1 NDRG3 ABCG2 TLN2 CTNNAL1 NETO2 MAPK4 LMTK2 HOXC9 PODXL2 TBKBP1 DTNA SOGA3 KIAA0284 ABCA5 VEGFA signal transmission NEURL HHIP ETV1 INHBB TOX3 SLC45A3 PPP1R13B CPNE4 RAB30 LARGE UNC5B NRGN SLC2A3 BCAT1 FN3K MDP1 ARMC8 SPRYD3 AGAP1 ICA1 AGAP3 FAIM2 SYT3 BNIP3 CABP1 EEF1A2 CDKL4 NEGR1 NETO1 GPR149 AHCYL2 RLBP1 ACSL6 MACROD1 RUNX1T1 PCDH18 SPHKAP signaling process EML1 RILPL1 RIC3 RC3H1 ZRSR1 ANKRD40 TMEM130 NACC2 PTPN3 TMEM14A ZFPM2 FAM8A1 SNCB SEMA3G WNK2 MAST4 ZFHX4 SYP MAP7D2 TMEM59L ASIC2 PPME1 SUSD2 SEZ6 TEF IGSF1 TTC1 GFOD2 CMAS SATB1 SLC25A14 SLC38A1 TRIM23 RALYL SDR39U1 ANKRD55 ANKRD6 SMARCA2 JAKMIP2 CDKL5 PGBD5 SYT11 NEFM NRXN3 CHGA STARD4 TMF1 PPP2R5E GSPT2 CIT REEP2 ASAH2 GBA2 TFDP2 CBX5 CSPG5 SDC3 NEFH CNIH2 MAGI2 TUBA8 CAMK1G GPLD1 FADS1 BAG4 MADD DST SPAG5 RPS6KA6 PTDSS2 KPNA1 SNPH ETNK1 PHOSPHO1 ABLIM1 signaling ABLIM3 FLT3 HABP4 DDC HEY1 MFGE8 CDH11 NPEPPS CTPS2 KCNJ16 PNPLA8 TSHZ2 ACSL1 GLRA2 MEIS2 CHGB CCNC GGT7 MTMR4 PTGDS FAM213B SCD SCG2 ENPP2 THY1 GLRB GLRA1 PPP2R2B HTR2C PDS5B PLA2G3 SLC24A2 RSRC1 LUC7L ZBTB4 SPOCK1 SLC6A1 TUBB3 ion transport HOXC8 KIF21A CACNA2D3 NECAP1 HLF SPARCL1 CLDN10 ASB1 DACH1 SIPA1L1 GPR158 ATCAY SCN1A PRODH SNAP91 EBF2 FGF12 FGF14 SERPINI1 ELAVL4 FBXO2 PPM1F INA ATP6V1A MYT1L ASH1L PREPL DMXL2 RASL10B SLC3A1 PFN2 CADPS NNAT ACTR3B DDX25 BLCAP APBA1 PKNOX2 KCNJ6 APC2 BCL2L2 UPF2 TP53BP2 THRSP SYT12 RIMBP2 USP33 MEST AVEN ARAF BTBD2 CA2 SEC22C LIN7B MPP6 CYP7B1 HSF4 RCN2 PHOSPHO2SH3GLB2 KHDRBS2 PDXP TSPYL4 HDAC11 SLC17A6 NAP1L3 GHITM UBE2E3 PTPN4 FAM188A SIX4 RAB40B PIM2 CNTN6 SST regulation of neurotransmitter levels NAP1L5 LNX1 NBEA MAB21L1 EFHA2 SIRT5 PLEKHM2 AKTIP MAP6 SYNJ2BP DNAJC12 NRN1 DSTYK KLHDC3 SYNE1 ATP2B2 PPP1R1A RNF14 MYH10 KIF26B NFE2L1 CDK14 WDTC1 NELL1 EPN2 PRPH CLCN3 GPM6A CKMT1B GAS2 LUZP2 UNC13C KIF1A CORO2B SRPK2 PTPRN2 ATG2B metal ion transport DCUN1D2 CIB2 TRIB2 STMN3 PLCL1 NRG1 BCL11B DKK3 ID4 PJA1 NDN MAST1 HOXB6 MTMR7 SGTB MAST2 SLC7A1 TRIM37 TTC3 EPB49 TESC USP32 HIGD1A TCF25 GPRASP2 HERC2 PJA2 OLFM1 PRRT2 PNKD RAB6B KCTD3 SLC7A10 NDRG1 GDAP1 ADAM23 TMTC1
GPRIN1 PITPNM1 COCH SLC22A17 DCLK1 RBFOX2 LRRC58 LRRN2 JAKMIP1 RTN1 RTN3 APBB2 MYH1 EXOC6B PPIP5K1 LINGO2 TCEAL1 LRSAM1 LRRN3 LRRC4C LRRC24 LRFN5 TRPM3 RBFOX3 Sep-03 ATP8A1 KIFC2 PGRMC2 ACTR10 SCD5 SYN3 POU3F3 TXNRD3 SGSM1 RUSC1 WNT7A GPR37 CDK14 potassium ion transport RUNDC3A NSDHL CHN1 TRPC1 GRM1 ADCY3 RASGRF2 SCN2B SCN3B RAPGEF3 GABBR2 PPP3CB RAP1GAP LDB2 SSBP2 GABBR1 RASGRF1 KCNC4 CLSTN1 MMACHC LMBRD1 AQP4 KCNJ10 PEX19 ABCD2 PDE10A CACNB2 SCN4B GNG13 CACNA1B EPB41L1 SPTBN1 FGF1 PLCB1 PRKCE TUBB4A PLCB4 cell communication GNA14 CLASP1 RGS7BP CACNB4 DSCAM CPEB3 TOB1 PDE2A SLC32A1 PIP4K2A PRLR CDC42EP2 FGF9 DYNC1LI2 SV2B GRIA2 CAMKK1 PEX5L NKD1 CALM1 UCHL1 EPHB6 DPP6 CNTNAP1ARHGAP44 GNAO1 ENTPD6 ENTPD3 KCNC2 CDH10 KCNQ5 CNR1 PDHB CDH7 PCLO MUT CYP26B1 ACTR10 ALDH1A1 RIMKLA PPP1R1B HSPA12A NAT8L CDH6 AK1 HNRNPA3 PCBP2 CDS1 AGPAT3 GLS GLUD1 ASPH HOXA5 KCNAB3 AKAP10 RASGRP2 SLC12A5 SLC5A7 HAP1 AHI1 DNM1L YWHAG NAPG NSF ACSS2 ATL1 REEP1 RGS17 GNAZ NDUFS1 GSTA1 MGST3 DNAJC5 FGF13 CLTB cation transport DNAJC6 LPIN1 CHPT1 SLIT2 FAM103A1 RNMT CPLX2 DEPTOR KCNS3 AGT TRIM32 NLGN1 PKP4 DGKB DBP KCNC3 ADAM22 GRIA3 RAP1GAP2 PDE1B MRAS DNAJA1 CALB2 PVALB NFYB AACS PRKG2 TAC3 PLCD4 MAP4K2 RIMKLB SYN1 ALAS2 STXBP5 GNAL FBXO9 NPY1R neurotransmitter secretion PTPRR TCEB1 GPT2 FBXW7 EGLN3 SCN1B KCNJ11 SHANK2 CHKA ARL6 ELOVL6 KIF5C TRHR RGMB PI4K2A ARHGAP21 SMAD9 SIN3B BRMS1L PGM2L1 ARHGEF17 MECOM DNAJA4 CADM3 ENAH PIP5KL1 MPP3 PLXNA4 NTRK2 EZH1 OMG LINGO1 FRS3 NAPB NR1D2 RORB GRIPAP1 monovalent inorganic cation transport GNG8 CBX7 MAPRE3 PTPN5 INPP4A FBXO44 SHISA9 CBX6 AMPD2 PTBP2 MATR3 RCAN2 L1CAM CAP2 SPTBN4 KLHL8 RRAGB HECW1 NPY5R AK4 MAP1B SPTBN2 NOS1AP ACSS3 GABRA1 ECHDC1 MBOAT2 STMN2 GABRB1 NCKIPSD CTNNA2 PDE4DIP FBXO32 GABRA5 LGI1 KHDRBS3SLC25A12
UBE2QL1 CCL27 FAM13B FAM13A AUH GABRA2ADCYAP1R1GABRG2 GDI1 GABRB3 QDPR FASN EPB41 RAB6A DGKE SENP2 RANBP6 PPP4R2 INPP4B DGKQ SHANK3 GRHPR PGP NGFRAP1 RGS5 ASS1 TBCC FNBP1 RHOT2 ACYP2 FEZ1 ATP2A2 DAO BRSK1 MAP2 CDC42BPA GRIN2A regulation of neurological system process ITSN1 CDC42 PRKACB PRKAR1B KIF3A KIFAP3 FLT1 EFNB3 PAK1 VEGFA KIF5B PAK3 SSTR2 SST SNAP25 CPLX1 DLG4 CACNG2 KLC2 KIF5A CUL3 KLHL12 PSMC5 PSMD12 SPAG9 KLC1 GNB5 GNG2 EPHA4 EFNA5 ABAT UBL4A USP13 SPTB ARHGAP32CNTNAP2 CNTN2 0.000 0.005 0.010 0.015 0.020 ALDH5A1 BBS4 BBS2 VLDLR DAB1 PRKCI GNG3 RPH3A RAB3A TNK2 BTRC GRIN1 DLGAP1 SCAP INSIG1 CRY2 SREBF2 SMARCC2 CYP51A1 MPP5 INADL SMARCA2 PARD6A LSS SMARCD3 SYT1 HSPH1 USP46 WDR20 RIMS2 RAPGEF4 STIP1 RGS7 RYR2 NCOA1 HMGCR FKBP1B
NALCN DOCK9 THRA UNC80 AGL MAPK8IP3 MAPK8 MEIS1 HSD17B7 MSMO1 RIMS1 PYGB BBS5 KCND2 KCNIP1 ANK1 HOXA9 PRKACA PDE4D SSTR1 HSPA4L HCN1 HCN2 SNCA SLC9A3R2 PHLPP1 SC5DL FDFT1 ACLY GRIN2D RAB4A RABEP1 NFATC2 HMGCS1 UNC79 MCF2 KCNAB2 0 Betweeness Centrality 30 60 90 KCNA1 STX1B STXBP1 APLN THRB DHTKD1 APLNR TUBA4A TUBB3 EPHA5 KCND3 ARHGDIG MAPT SQLE GRIN2C PDRG1 PFDN2 PGR AKT3 TSC1 VAMP1 FXR2 CYFIP2 ATP1B1 NECAB3 APBA2 NPAS2 GRIA4 ACAT2 ADCY2 GNAS NRCAM ANK2 IRS2 MCF2L PFKM CLOCK 120150180210240270300330360 MAPK9 HK1 GUCY1A3 GUCY1B3 SIRT3 PPARGC1A RGS4 GNAI1 KLHL20 CAMK2B ZWINT ME1 GAD2 TTBK2 SCN2A ANK3 ME3 MDH1 PYGM GABARAPL1 GOT1 IDH3A MAP1A AKAP6 ULK1 FDPS FXYD7 Sep-06 SLC18A3 CHAT ATP1A2 Sep-05 Sep-08 ALDOC SUCLA2 MVK KCNIP4
S1PR1 SYBU GAD1 MARK1 ATP1A3 ADCY5 DNM1 DYNLL2 DYNC1I1 SHANK1 EPB41L3 CCK ARHGEF4 PPP2R5C PACSIN1 NDUFA8 NDUFA7 MYRIP TAF1 TAF9B PPP2R2C SYNJ1 SH3GL2 LDHB SMARCA1 ANGPT1 GRIA1 KCNH2 IDI1 SLC12A6 STK39 ARHGAP35 RND1 PCSK2 RGS6 MVD SCG5
NPTX1 OPA1 ENY2 KLHL7 RNF8 UBE2V2 PRKAA2 NCS1 BSN PPP2R3A PNOC PENK CACNA2D1 CACNB1 CLPB KCNC1 RAB27B TRAK2 GABRB2 MAPK12 GRM3 ADCY8 ABI2 PPP3CA EBF1 ZNF423 KIF3C DPP10 KCNAB1 ARHGEF25 RHOF ESRRG Number of Genes
G 700 H 0.005 JUN NFATC1 600 0.010 500 0.015 0.020 SP1 400 0.025 300 0.030 value (gene array)
200 p
Number of Genes of Number 0.035 100 0.040 MAZ T-test 0 0.045 0.050 SP1 JUN MAZLEF1TCF3 PAX4 0 2 4 6 8 10 12 14 FOXO4 NFATC1AACTTTREPIN1 Fold change (INJ/CON gene array) Key transcription factors u u u u Supplementary Figure 2
SALAMANDER 7D UPregulated Genes UPregulated Genes A MED31 GNGT1 GNB5 ATP6V1B2ATP6V0D1MAP1LC3B ATG4B PKM TPM2 ATG3 ACTN2 ATP6V1C2 ATP6V1A PIK3R1 KIT MST1 MMRN1 TUBB3 CFI C3 HSPG2 EEF1A1 TUBB4B TUBA1A ENO1 MFAP5 COMMD8 ECHS1 PGK1 TPI1 TUBA1B TNNC1 TNNI2 TNNT1 RPL3 E BIOLOGICAL PROCESS RPL27 F5 ABI1 KLC1 KIF5A NEB TTN MED18 MED30 NRBF2 ENO3 EPS8 TNNI1 BECN1 ATG14 INMT RARRES1 PSCA TMEM37 PLAC9 IAH1 C5 CDH11 HAO1 EPHA2 SPTB SLC2A2 UGT1A9 CYP2B6 AVPR1A RECK PGM1 PGM2L1 COL6A2 MYL4 C
PRDX6 FBLN5 C7 ALDH1A3 MLC1 KDSR CERS1 HOGA1 ACTA1 HEY1 HEY2 MAOA DDC PFDN1 CYP3A4 THBS3 FBP2 MYOZ2 MYL1 AMACR CHST5 NTS ALDH1B1 EXOC6 MYH4 MYH2 CHGA LAMB1 MYH8 ADH7 MYH10 ALDH1A1 ADH4 SCG3 SLC4A4 ST8SIA2 GSTP1 CA2 FLNC MYOZ1 BCAN MAP3K7 CDH13 MRPS7 MYBPC1 CDH17 SPR PTS DPYS UPB1 ITPA ADSS DES SGCA NCAM1 MYBPC3 JAG1 PWP1 C9 SGCB CAT CD59 MAP1B PFKM SGCG TUBB2B SPTBN1 ADSSL1 MYL3 ACOX3 Most central Genes CTSG AGT NPY PMCH SOD2 HBA2 HBD EIF4EBP1 HSD17B4 CRMP1 MUC5B MYH7 MYLK MYL2 LRP5 CDH2 GCG PAX6 ASAP1 ARF1 ACAN MFAP2 FBN2 LRPAP1 LRP1 MYH3 TRIM63 COMMD10 LDB3 MYH6 CD74 CTSS MUC4 ALDOA SOD3 muscle system process MUC2 GZMB SRGN EIF4A1GABARAPL2 KIRREL CFB ACTC1 ATP6V1G3 GPR34 CALHM2 LEPROT LRRC8D SCPEP1 PLGRKT ALDH2 TFPT PTTG1IP QSOX1 PTPLA DSCR3 LAMA4 VPS13C PRSS23 TMEM86A CTHRC1 LMCD1 TMEM176B OLFML3 PXDN SGCE PEPD ABHD12 NPRL2 LGALS9 muscle contraction XYLB AGTRAP VAT1 TRIM27 AIF1 MRC1 GPNMB SNX7 CNPY2 PLBD1 TAGLN CDK20 GAMT NAT1 PLIN2 LGMN AP1S2 LAMP2 LITAF STOM LOXL2 BTG1 HIST2H2BE PAOX SERPINF1 ORAI1 EIF1AD MCAM COMMD7 SERPINH1 MAN1C1 COL3A1 HBP1 RBKS PDLIM7 CAT COL12A1 CPT1A ZEB2 ARAP1 PTPRO COL6A3 COL5A2 COL6A1 RUFY1 C4orf22 NHSL1 STPG1 TTI2 IQUB SEC22A THAP4 LYPLAL1 TAF1B KIAA0232 FAM47E RFXAP SLC25A26 ANGPTL7 TCHP C1QTNF1 OCIAD2 PPDPF NKIRAS1 C12orf29 C18orf21 GPRC5B NEIL1 PCDH18 CA14 TRMT12 muscle structure development C1QTNF3 C1orf123 VSTM4 SLC43A3 TMEM45A FAM115C SCRN1 NDUFB1 FITM1 C8orf59 LYRM1 C1QTNF7 YAE1D1 IL17B CASC4 PXMP2 SUSD3 RAB42 IQCG KIAA1462 AUTS2 AADAC ANGPTL2 GPR37L1 B3GALTL GPM6B LYPD6 TSPAN18 ARPP21 BPNT1 INO80C MSS51 OXR1 THBS4 TRIM15 DNAH8 striated muscle contraction METTL15 WDSUB1 GALNTL1 CTSK KLHL15 POSTN CACHD1 DTWD1 BTBD17 LOC388210 ROGDI CCDC173 FBXL8 RIIAD1 MYCT1 TM6SF1 FAM117A TRIM39 SLC18B1 IGSF21 SOBP MSMB KCNMB2 VWDE CSTB MURC WFDC2 FAM208A CTXN3 CTXN1 CISD3 C12orf49 KAZALD1 FAM214A CCDC169 small molecule metabolic process RASA4 C9orf116 PLEKHA5 SLC51A ERI2 C12orf52 TRIM35 C3orf14 C1orf177 CADM3 COL6A5 DPY19L1 CYTL1 C7orf55 MCTP1 CCDC69 TXNDC17 CHODL MR1 MAMDC2 TMEM64 PKIA VAMP5 METTL7A RNF125 STXBP6 RWDD3 ITGBL1 FAM32A CERCAM SYT4 CRYZ SERAC1 EMILIN2 SORCS2
NID2 DUSP18 NEK3 RAB2B LAMC1 CLVS1 CLYBL NDUFAF6 PIEZO2 C4orf33 RBM43 TXLNB GPR137B NAT16 PDZK1IP1 SLC39A3 LMBR1 NACC2 ZNF26 ZNF84 ZNF418 ZBTB1 OSR1 ZNF510 ZNF568 HADH ZNF391 ZNF248 ZNF25 ZNF235 ZFP3 RAPGEF2 ZNF133 TEX11 HRC ZFAND4 extracellular structure organization PRSS16 NXPE3 ATF1 DST COLEC12 LHFP RGS5 ZNF567 ACAD11 WDR47 ASRGL1 CNRIP1 OGFOD1 CAPSL RBM12 STON1 FN1 SESN3 ZNF548 ACSS3 C2orf62 CEP97 SLC16A2 ACTA2 DNASE2B TSPAN1 NKAIN4 SYF2 DCT CCDC174 SDSL MACROD1 JMJD7 SLC38A9 ZBTB33 muscle organ development GJC1 MTCH1 P4HA2 TMEM55A ARSB UMOD LRTOMT C6orf162 CCDC117 TNFSF12 BCO2 SPATA7 DNASE1L3 RFTN2 ARHGAP24 C14orf28 LUM TMEM69 CKAP4 TMEM2 IGLL1 LYPD2 TMEM74 ATHL1 XRCC2 TMEM79 DNER GBA IGJ EOGT C3orf33 GLOD4 MRC2 IDS SEMA3D ACTA1
KRT15 TC2N TMEM182 IRGC SUSD4 SNCG MDGA2 POP7 PDK2 LAYN ZBED5 OLFML1 PGBD5 CYP27C1 REG4 DUS4L PCBD2 FLCN GPATCH1 RUSC2 BTBD2 CCDC92 EPDR1 ANXA1 PIR TEKT4 SCFD2 CD109 C8orf82 NIPSNAP1 CRADD C1orf192 OLFM1 GPM6A NOSTRIN extracellular matrix organization
CRISPLD2 GDA OLFML2A XDH NSMCE2 ZNF777 ALG6 COQ3 ALKBH2 NUDT7 NUDT19 TERF2IP MXRA5 DAB2 RSPH9 RGN DGAT2 ZNF467 ASPN NLGN1 SPON2 PCDH15 EBF2 CLEC11A P2RX5 PPM1M SLC13A3 ZNF414 TTYH1 RSU1 DUPD1 TSHZ1 DCAF6 LPHN2 TTYH2 KIT oxidation reduction GLB1 ANKRD16 ENOSF1 MSI1 CCDC80 REEP6 FMN2 SLAIN1 SPECC1 HOXD10 XRRA1 CHRDL1 RASL11A C21orf2 CCDC19 RHCG ABCB5 FAM110B NDRG4 RIBC1 MAN2B2 C12orf4 FAM189A2 FRG1 DHRS7C SMTNL2 SULT1B1 FAM96B MLF2 COL1A1 DNAJC21 SLC24A2 DIRAS2 LRRN1 MARCO regulation of ATPase activity PRKRIP1 TRIM72 PYCR2 SERPINI1 GDAP1L1 CLN5 TMEM100 TMEFF2 BCAP29 CD207 LINGO1 PTPRM PCYOX1 FKBP11 SLK THAP5 ZNF326 COL5A1 SH3BP5 C19orf70 CRABP1 C18orf54 CMBL TMEM183A NIT1 MAN1A1 ANKRD29 LGALS1 ZFAND2B SULT6B1 THBS2 CBR4 PLEKHF1 CACNG1 ENPP5 ENO1 SVEP1 UBXN11 TEX30 TNC CCDC88A SLC13A2 ASB13 AARSD1 GGCX MCC F10 DPT CD300LF PSME4 BDH1 SLC7A10 SQRDL PTGR2 DCUN1D4 GRN ZNF407 SMPX PACRG LPHN3 UBAC2 CLCN5 FCN1 LRRC18 CPQ JPH2 C16orf45 RUNDC3B HSD17B8 KIAA1107 DZIP1 monocarboxylic acid metabolic process ALKBH6 CA3 NUDT18 FUT11 THNSL2 METTL21C FBN1 SOGA2 PROS1 WBSCR27 D2HGDH TICAM2 SNAP47 MGMT SLC17A6 HGFAC HLA-E RCOR3 PLSCR1 ADI1 MTG1 CD248 ORMDL1 NAIP USP18 PKDCC RNF13 RNF24 REEP1 RTN2 RAD23B ARL16 ADAMTS12 ZC4H2 WDR16 CDH17 anatomical structure development ZBED1 ZNF593 KPNA5 FBXL18 AGMAT SLC25A46 CDC123 PCMT1 YPEL3 SEPP1 IGFBP6 BHMT MTR STK39 ALOX5 AAMDC TFEB LMO1 S100A4 TTC21B DLK1 OLFML2BTMEM106BHSD17B14 IYD ZFAND4 ABHD3 STMN4 LRP2BP HTRA1 TFF3 RABL5 P2RX7 KCTD1 NOV cellular ketone metabolic process ITIH5 MAP4 UBE2E3 QARS PNCK KLHL31 IGFBP5 TMEM38A HMG20A CSRP2 TMEM178AFAM19A2 SLC16A9 GTF2IRD1 SETD9 FAM21A KLHDC2 TPPP3 GFAP CCNG1 GJB6 TEKT2 LMOD3 NEXN TMPRSS2 REV3L CALML4 CNOT6 SNCB MYEOV2 FBXL2 SYPL2 THNSL1 CYP4B1 TLR2 TF TTC30B SESN1 KBTBD5 RNF216 RNF19A CMYA5 NEBL CBLN1 SLC6A13 VPS33B PRPF38B HSPB11 RIC3 TP53I3 MTX2 CHCHD6 ZNF268 CYB5R2 SLC47A1 GYG2 CPVL AIFM3 FABP2 SLC7A11 DHRS4 NPTX2 DNTT HMOX1 LRRC71 C6orf118 YPEL5 EML1 SCGN C1R ZADH2 system development LRRC20 SDF2 PRG2 LAPTM4B PPAPDC3 MPP1 NRP1 SPRTN SEMA6A TMEM50A C9orf72 FBXW4 DPCD FAAH DECR2 COL4A1 SRL COL4A2 COX7A1 VIM FAP GLRX2 ARL6 FABP3 TENM3 CA7 TECRL DYNLRB2 ZNF521 CPB1 SERPINE2 TCF12 HSPB8 XXYLT1 CPE regulation of biological quality TMEM27 MYH7B MYBPH GXYLT2 MYO18B PTPN9 HYI SATB1 ANXA6 PVALB CETP NR2F1 ADD1 CECR1 HBG1 PDCD11 ICAM5 ADAL ITGAD TRMT2B APRT LMO3 RAB28 GPR125 NCBP2 CRIP2 GAS2 CNN3 CHRNB1 ABCA1 SUFU ANXA13 TPM1 GLT8D2 BGN CA2
GMDS FOXC1 TOX SLC25A6 METAP1D MMP16 RINT1 SPEF1 COL1A2 BIN1 CNGB1 SH3BGR CRYAB STRA6 MEST RBP1 HAPLN3 FBXL14 ABI3BP RTN1 HOXB9 WDR69 CASQ1 POLD4 HINT2 SPAG6 EFHC1 WDR45 HOXB7 HSDL1 ANP32A SYNC MYOM2 NACAD RAB12 organic acid metabolic process RBPMS TUBA3D RASEF RAB40B CDK14 ATP1A1 PTPN2 LRRFIP1 PACSIN3 CCNI CCDC104 TEKT3 SLCO1A2 MPP4 EIF4A2 SORD EVC2 TCEANC USP28 SLC13A4 MMP17 PON2 PDZRN3 BOLA3 KCNAB1 ARL6IP5 SELENBP1 RNF7 ABTB1 LGI1 PEG10 IL10RA S100A13 KIAA1217 CPPED1 ENO3 regulation of system process FAT4 Mar-01 GPD1 ZNF462 FSD1L SNX25 BASP1 GAP43 TXNL4B RDX ERMN TPM3 GPR133 SERPING1 NPPC RUFY3 FOXK1 WWP1 PDE8A CHRNA1 SCNN1B DKK3 GUCY1B3 KLHL7 KLHL3 CPA3 CYP7B1 CGRRF1 ST3GAL2 BCHE CGREF1 MYH13 B9D2 RFWD2 TUB oxoacid metabolic process GNG13 PLA2G4C ENPP1 NAT2 DYNC2LI1 OSBPL1A FTH1 ARHGEF25 LHPP KBTBD10 CABLES1 PRPH DNAH8 ENKD1 C1QC SMARCA5 ATP12A TUBA8 CENPO OAZ2 TPR SNTA1 SLC26A4 CHGB PEX11A PEX2 TCEA2 AFMID SEC23A FGF12 MIA3 CDC42EP3 FGFR3 RNF11 PEX11G
MYOT CFL2 FBXL5 FHL1 ROPN1L FBXO25 ATP6AP1 OSBP RAB11B CRABP2 ECM2 PSIP1 SPA17 RHAG ANXA5 PLS1 ASH1L SMARCA2 CCDC134 TADA2A C5orf4 MYOM1 HSCB UCHL1 IQGAP2 KCNJ10 OGDHL SMOC1 DACH2 STMN3 ELAVL2 DNAJB13 CENPV ALDH5A1 SIRT5 carboxylic acid metabolic process GLUL CHRNE RBPMS2 COX6B1 COX4I2 OLFM3 HDAC10 ATP2A1 CAND2 SFTPD TCF4 PROM1 TNFSF10 CALB1 SLC1A3 C1QB CORO6 STMN2 NEFM BMPER SPOCK3 PRG3 DEPDC5 ADAMTS13 MLF1 APOH TECR ELOVL2 SFTPB ECH1 CLDN19 CLDN6 SRPX2 EEF1D AP3M2 actin-mediated cell contraction ZMYM2 FXR2 ZNF280D POGZ DBI NDRG1 CBX7 PCGF5 NUDT16 LAMA1 HSPA9 DNAJA1 RELN SFRP2 PCK1 PTGES PTGDS ADIPOQ CXCR7 TGFBR2 CUBN TF GALNT11 AMPD1 YBX1 CHN1 RHOU GMPR TMOD4 PPBP AK1 BNIP3 CYP2C8 SERPINA1 A2M
UPF3B ACADL LAMA2 LAMB2 PRDX2 PSMD9 DHRS3 CLU VPS72 MEAF6 RHOQ FMO3 PRKAB2 ATP6V0E2 CA4 PRKAG3 MYL6 S1PR1 HPX MYBPC2 KLKB1 ATOX1 L3HYPDH OGN UBE2E1 ST3GAL6 FUT9 SSTR2 ADORA1 C8G RASSF4 EXT1 ARSA SEMA6D CYP2A13 0.000 0.010 0.020 0.030 0.040
DAO RYR3 FKBP1B ROBO1 BCMO1 IRF2 MYOG ACSBG1 CTPS2 UGT2A1 PPAP2B EFEMP1 BSG NR2F2 F13B SMYD1 WNT2B NMRAL1 COMMD1 WDR45L CDH6 TLL1 CNN1 EPHA5 ASPA HSD11B1 ECHDC2 MMP2 HMGCS2 HNMT GRIK2 CASK APOA4 TYROBP ADAMTS2 0 GSTA4 CST3 SFRP4 FYN MYH1 SKA1 BIRC5 AK5 POLR2L AK7 PTBP2 CXCL12 EPHA7 ACY3 MYF5 CAPNS1 RDH16 NRCAM LTBP3 LTBP1 AGXT2L1 SBDS ARHGAP28 FIGF ICAM1 FGD3 SULT2B1 P2RY4 CHST11 SLC22A3 ABCG2 PEBP1 HAAO CSPG5 PYGM Betweeness Centrality 20 40 60 80 100120140160180200220240 PDLIM5 AGPHD1 Number of Genes
DOWNregulated Genes SALAMANDER 7D DOWNregulated Genes F BIOLOGICAL PROCESS BCARTPT LEP XPO5 ZNF598 NUP160 MAPK13 NASP UBAP1 LIN9ENSG00000243207YTHDC1 TK1 IFI6 MYH14 HNRNPAB SPEN TNIP1 MUC15 GCNT4 C1GALT1 PNPT1 BCL2L10 TFAP2A ARHGAP5 DSC2 SRSF12 IDH3B PKP3 ADAR PRPF39 GFPT2 GNPNAT1 EPCAM CLDN7 SEC24C DAAM1 PITRM1 BMP7 TAOK1 TPM3 CSNK1A1 ZNF259 HES1 TLE4 APLP2 PREB UPK3A SEC23B ITPR3 CBX3 SP7 RRAS TMPO PGGT1B MMP13 ADCY4 SYNE2 GBP1 CBS TSPO VPS37B GCM1 HERPUD1 PRMT3 UBE2J1 PKP1 DSP SCAF1 IFIH1 PNP D SHMT2 MUC16 MRPL4 MAP2K2 SERBP1 CENPF ANLN ITGA3 IGF2BP3 OAS3 ELL2 PTGS2 MTA2 NMRK2 ATP6V1G1ATP6V0D1 CLP1 MAP4K5 CIB1 LIMA1 CXCL10 IPO7 HIST3H2BBFAM115A PRMT5 DES ETS2 MUC4 MAT2A PSPH PCK2 EIF2A MYOF KHSRP DDX39A
CTBP2 RASSF1 CASP6 PELI1 STAP1 UPK1B RHOB UPK3B DNAJB9 KHDRBS1 MYBBP1A FUS SUZ12 OASL DNAJB11 MMP10 PEG10 ZFP36 SERPINE1 CAPN1 BMP2 MSX2 TMBIM6 ODC1 ARAP2 FERMT1 RAE1 IFIT5 BLNK COL11A1 B4GALT1 PPM1G COL2A1 GNMT SPAG1 nucleic acid metabolic process HCLS1 PDE12 SNX18 DSC3 RNF139 TXNRD2 HS6ST1 TFF2 TAT MAT1A EMX2 SALL4 ARHGEF16 CBX1 COL14A1 FAR1 MMP8 COL24A1 SGMS1 COL8A1 MRPL47 FGFR2 PBK GAK ATRX RNASEH2A DAPP1 CDCA7L SLC2A1 COL4A6 COL4A5 SDR42E1 KLF4 DUSP10 GMPPA Most central Genes cellular nitrogen compound metabolic process PMM2 EPHA1 NME4 SACM1L KLF2 CSNK1D SNIP1 MYL7 PRKAG1 KERA B3GNT7 TNFRSF21 PPARD DBNL WARS TIAL1 NME6 SRPR SEMA3A TPD52L2 ITPKC SLC35A3 GALNT4 PLK4 NOMO2 NR4A1 ARHGEF5 ALOX15BARHGAP11ABAIAP2L1 VPS13A SLC20A1 IFITM3 HIVEP2 VRK1
ALOX12B CYP2C8 CARS SDF2L1 XAF1 NOXO1 CDCA7 MOV10 TNRC6A LRRC59 ELF3 BATF3 MPO OGFR UGDH SLC35D1 ALDH18A1B4GALT4 B3GNT5 EPHB3 DDIT3 SKIV2L2 C1QBP MED11 CD69 ETF1 UGCG CERK ELL PRKX GPRC6A SUV39H1 EWSR1 FLNA CDS2 cellular macromolecule metabolic process SF1 DMD PPAP2C CANT1 CFD RBBP6 MIS18A RBM15B CD2AP RHOT1 INSM1 CCNE2 CABIN1 RAB1A NANS OCLN KIF11 MMP1 BCL6 FOXO1 ASF1B PFN1 HIF3A NARS DDX24 KIF20A G3BP2 CRKL NEDD9 E2F3 HIST1H1B RHEB HNRNPC BCL10 GADD45G UBC cellular process RNGTT FBXW5 TJP2 SRSF4 NR2C1 PRC1 YARS DDX54 SPINT1 ST14 YBX1 PGAM1 EIF4E ARHGEF7 GINS2 SRSF1 TRA2B EREG RBMX MYB DKC1 FBL WIPF2 WASL NCAPH2 NCAPG2 RPS6KB1 CCNK MMP2 STAT5A IRF7 WEE1 CASP1 ITGA6 COL17A1 nitrogen compound metabolic process ELAVL1 TIMM10 CHCHD4 SYTL4 RAB27A SNRPA RBM28 DNAJC10 MAD1L1 VHL FBXW11 CCNB2 IARS CENPA EFTUD2 SNRNP40 GRPEL1 SMC4 RBCK1 COPB2 COPG1 MMP3 EXOSC2 NOP2 TIMP1 HNRNPK RRS1 HIST2H2AC ECT2 GNL3 WAPAL TARDBP FEN1 CYFIP1 NCKAP1 TSPO
SNRPA1 USP10 MXI1 HDAC3 PLEC ITGB4 PARD3 EEF1E1 NCOR1 PRKCZ KRAS TP63 MARS UBE2C ANXA2 EXOSC6 FZR1 S100A10 NCAPD2 SH3KBP1 PSMD5 PTGES3 IRF3 CDH1 INCENP SMC2 CCNA2 RPA1 JUNB FOS FBXO5 RRM1 RRM2 ERRFI1 SDC4 macromolecule metabolic process TIAM2 MUC5B RHOU PACSIN2 DNM2 GPN1 GPN3 EXOC5 RAB11A UHRF1BP1 RAB10 UTP14A EGR1 EXT1 EXT2 PIM1 CYR61 ITGAV RPS6KA1 DHFR RRP1B SLC16A1 UTP18 RFC2 SUCLG2 PDE4B HIST1H2BJ UPP1 JUP PRTN3 SPI1 UCK2 HYOU1 PPM1B PRIM1 ELAVL1 cell cycle RRP1 LPAR3 CDK7 KIF15 AP1B1 CLINT1 LMNB1 RANBP1 KPNA2 ID2 MX1 CANX YARS2 USP4 RNF19B UCKL1 AREG HSPA1L DNAJC3 NEK2 SDC1 NOLC1 SPTLC1 CCNB3 PLK3 GADD45B TTK NAT10 CTCF CHORDC1 IGF2BP1 SLC1A5 HM13 G6PD TARS TJP3 PSAT1 CHMP4A SLC7A5 DHX15 ACSL4 PLK2 HMBS ALAD HNRNPM BLMH NAPA PDE6D USP19 TUBA1B CASC5 HLTF CIRH1A WDR75 DUSP1 SOCS1 IRF1 ILF2 CENPQ LBR CCNO MAP2K3 MAP3K5 CCND2 MAPRE2 LEF1 ETS1 THBS1 POLR1A MRTO4 MYC mitotic cell cycle CDC5L TOP2A RGS2 GNAQ CUL4A TACC3 NGFR RPS6KA3 VAMP7 NTF3 FBLIM1 VASP SRSF5 SRSF7 TGIF1 CTBP1 HIST1H1C TANK SRSF3 SYTL2 RCOR1 REST SUGP2 PLCXD2 MAL AAED1 MFSD6 FAM84A MAD2L1 RACGAP1 RAC1 IQGAP1 MAD2L1BP EGFR IL13RA1 cell cycle phase IL4R U2AF1 MCM6 CHAF1A HSPD1 HSPE1 UBB GRPEL2 HSPA9 CDK9 SUPT5H CHAF1B BRD4 BRCA1 ESCO2 CTDP1 MRE11A RPL14 RPL31 HSPA5 CDT1 EIF2AK2 PRKRA HSPA8 DNAJB6 LDLR PCSK9 ISG15 HERC5 IL1B IL1R1 TPX2 AURKA PDPK1 CDC25A EGFR primary metabolic process MED15 SGK1 SFPQ NONO CCNB1 KEAP1 VPS4B CHMP1A GOSR2 STX5 HSP90AA1 MAX CHMP6 VPS36 KLF5 CXCR1 IL8 MYC NDC80 BCL2L1 APAF1 ARRB2 HNRNPA1 PTBP1 SHISA4 BIRC3 NFKBIA USP7 UBE2D2 PCNA KIAA0101 MDM2 UBC CDK1 CDC25B ORC1 MCM7 AURKB KIF23 MCM2 CDC6 SRSF2 ACTN4 ACTN1 MCM10 PLK1 CDC20 MCM5 ORC6 MCM4 GADD45A MCM3 NCBP2 NCBP1 NIPBL SMC3 CUL1 TLCD1 MIA3 ITFG1 CHCHD10 STRBP ABCB9 FAM98A SACS NCOA7 TRIM16 FAM110B ALG2 NEK7 KRAS regulation of cell cycle STARD10 TMEM50B PELI2 SNX10 KIAA0664 PPTC7 SLC30A9 WHSC1 SYT16 ACOT7 SLC38A2 MDP1 SPRYD3 CMAS DST HABP4 MPP6 MAS1 SOWAHA FCN1 CDH26 MEDAG FLRT2 BTNL9 MFSD7 TPRN GHITM RTP3 GIMAP7 PTPN4 FCGBP GTPBP2 SLITRK6 KIAA1704 CPAMD8 M phase of mitotic cell cycle NXPE2 DNASE1L3 LNX1 GPA33 SDCBP2 RNASE1 SLC52A2 CCRL1 TMEM181 ZDHHC15 C1orf116 FAM26D MACC1 MFSD6L C17orf67 TMEM45B SLC17A9 ADAM28 AIM1L MYH10 CCDC174 SLC10A7 SLMO2 RBP7 CXorf23 TTC22 PPP1R26 TMEM52 CCSAP EMP1 DENND2D PHLDB3 DSEL S100Z ARRDC2
CALHM1 PSCA KIAA2026 FAM101A TMEM44 PRRG4 R3HDM4 KIAA0247 TMEM123 MFSD11 PRLH POF1B ESM1 TMEM180 FAM107B SLC7A1 USP32 SLFN13 CLDN4 KLHL11 TMEM79 TSPAN15 C10orf47 XK TMEM51 TMEM168 TRANK1 GDPD3 GPD1L PARP16 NABP1 STK17B PRG4 SSUH2 SLC35B4 HSP90AA1 nuclear division
ZMYND19 NYNRIN VIL1 C9orf3 LACC1 SSBP2 SEMA3F FUCA1 KRTCAP3 MMD RAB38 DONSON SLC25A39 CSRNP1 AQP4 GCOM1 ZNF574 TSC22D2 CA5B RBM24 WIF1 MYO3B RAB5C PRICKLE2 CYP2C18 MAN1B1 PHLDA2 WBP1L HEATR3 TIPARP HIAT1 NAA30 SWT1 ZDHHC7 BSPRY mitosis HMGN5 GIMAP4 RBM6 C2orf40 PLEK2 TMEM2 RBM33 PADI4 DYNC1LI2 SPSB4 ST8SIA1 FASTKD1 TECTA ZNF750 CAPN9 SAMD9L CRLF1 KATNB1 ZNF185 IFRD1 PPP1R14B FASTKD2 SLC7A3 SLC16A6 CHCHD5 BCAS1 AGR3 METTL20 EPPK1 MOXD1 TMEM208 IRGC ZNF182 ZNF572 SFMBT2 UBB cell cycle process FAM76B NBEAL1 SULT1C4 AVIL TMEM251 MRM1 NFKBIZ TRIM39 CDS1 C6orf136 FCN2 GJB5 SURF4 TBC1D12 FAM102B NCCRP1 FGFBP1 SLC31A1 ZC3H10 ST8SIA6 IPPK KATNBL1 CCDC167 GPR84 SERINC5 VIT GPR64 PRSS27 TMEM120BHSD17B2 RAD51AP1ANKDD1A IFITM5 CLIC3 TMEM154
GPR116 GJB7 HARBI1 C12orf43 DHRS12 CNP FAM103A1 RTL1 CARD6 SHF ANO9 SFSWAP APCS EPSTI1 AVPI1 C5orf30 FAM115C LRTOMT C14orf37 EHF SLC20A2 WDR4 POLR3C MRAS EIF4H NBAS CALB2 VKORC1L1 NFYB C3orf38 HNRPLL MMP28 ZC3H11A SSFA2 CCDC43 ISG15 cellular metabolic process STX11 RIMKLB MAPK6 CYB5R4 Mar-03 PHF20L1 PPP1R15B KBTBD2 GLTP CAPN7 MTSS1 GPT2 FBXW7 STRN3 MB21D1 HNRNPH2 SMAP1 FAM83B REEP4 CHKA USPL1 KRT4 ELOVL6 TGM3 ZCCHC7 EPX TWF1 CYP4F22 NR4A3 SLC39A7 PPRC1 PUS3 PADI3 TFAP2C METTL2A organelle fission TNFAIP8 ALKBH1 MRPS27 GPR87 PLEKHG4B RBM47 ELOF1 WDR76 F13B ZCCHC8 BCL7B RHPN2 CAPN13 ARL9 ANKRD50 PNISR ABCB4 FYCO1 STAM DLX6 CPT2 NUAK1 DIRAS2 TMEM63B RHEBL1 HEBP2 MIDN PPHLN1 TMEM127 HIATL1 SIPA1L3 PARP12 PRSS21 IFRD2 TMCC1 MYH14 RNA metabolic process CDC42BPG SPTBN2 ZFAND2A BRD2 TESK2 ARL11 VWA5A ELOVL7 ENPP4 H1FOO OVOL2 CMKLR1 IVNS1ABP CRELD2 RBM45 ABCB10 HOXA13 DHRS13 ZNF318 TWF2 CREBZF PTPRZ1 IL17RA BCAM TRIOBP EMD ERMAP UMOD LAD1 TOB2 SPATS2 OTOF DNASE1L1 CLDN3 MPV17L2
RASSF6 DISP1 CLCA2 CHST14 PGP CDV3 ZNF398 SLC9A2 RNF144B CYP4B1 RPUSD2 HSDL2 C4orf27 CCDC71L ATP2A2 HOPX GRHL1 SULT1C2 FICD PNN NUPL1 TRABD TYRP1 BCLAF1 CPOX NOM1 TPD52 NKRF NFIL3 VMP1 PRPF4B EYA2 F3 TGM1 KRT12 M phase SPRED1 NPM3 KDM4B SERPINB5 SEMA4F MYCL1 MCU ATAD2 ATF5 TNFRSF12A ZNFX1 COQ10B ADCK3 CDO1 YLPM1 E2F8 CMSS1 RRAGC AQP3 EPN3 PALLD LAMB4 CCNI2 TNFRSF6B GRHL2 PANK2 ZNF703 AQP1 BNC1 MANF MATN3 OTUD1 TNK2 PAPD5 CARD16 metabolic process YIPF6 MTPAP HTRA1 MLL3 LMO7 TREX2 MGAT2 CYP51A1 TMOD3 DOT1L BAZ1B PAPOLG FAM18B1 PKNOX1 ADAP1 PIP4K2C TRIB1 MFSD1 TCOF1 KRT15 PARP14 TNN DNAJC9 SMYD3 ACSBG1 HMGCR KRT76 PCSK5 KRT71 ANKRD2 GOLT1B MEX3C IL20RB RBBP9 FAM108A1
ATAD3A CLEC3A MSMO1 ACSBG2 ADPGK ATP1B2 OPTC RNF213 ESRP2 CLEC2B EFHD2 PRKACA RETSAT PDE4D FAM136A GRHL3 OSBPL2 TM9SF3 PRR11 BTBD10 ALCAM TSPAN3 DNAJC15 BCAT2 ACLY PHF6 ARL4D ISG20L2 MGAT5 ZIC1 HMGCS1 RHBDL2 NUSAP1 PRRC2C JOSD2
PMEL SLC35C1 ARRDC1 FRK DLG3 OTOA MALL SLC2A5 UBAP2 TTC39B XYLT1 TCHH TGM6 SQLE LGALS3BPMARVELD2 LIPG PNLIP LARS2 PDLIM5 KRT5 STRADA KIF22 BCL9L ERO1L TRAM1 PITPNB PVRL2 ZRANB2 UBIAD1 PLA2G7 C5orf15 ANTXR2 ENTPD2 LRRC47 0.000 0.050 0.100 0.150 0.200 0.250 0
DUSP5 FBN1 CYSLTR1 SLC25A32 ETV4 DRAP1 PLA2G4C BOD1L1 PLIN3 NT5C1A CFP F2RL1 DCK PTCD3 FAM3C LMNB2 CASP5 CAMP CBFB TRNAU1AP PIM3 LPCAT1 COL21A1 PI4K2B REP15 TNFAIP1 KRT17 SPOP FDPS PDLIM2 PHRF1 PXK LIMS1ST6GALNAC2IGFBP2 80 160 240 320 400 480 560 640 720 800 DCTPP1 Sep-08 RAPGEF6 MTBP CBR1 MVK MELK KDELR1 HK2 NNMT F2RL2 CAMK2D SLC30A1 RBM14 ACY3 CPSF3L DYNC1I1 TNKS1BP1 SASS6 EHD4 KRT2 ARHGEF4 PDLIM7 CNDP2 COL28A1 DEDD2 HMGA2 SORBS3 CASP10 HID1 GCLC CELF2 NUCKS1 SRRT LARP4 Betweeness Centrality DAPK3 RRAD COG3 DERL2 HBZ MPZL1 YTHDF2 SEC14L1 CPNE1 CHTOP CCNL2 PRPF31 EVPL LUC7L3 TDG UAP1 LATS1 TEAD1 FBLN1 HELLS PRDX5 TMEM209 HSH2D UPK1A PUF60 TRAF5 SMARCAD1 PARP9 RAB27B TFPI2 HERC6 MYO1B MAPK12 HAS2 LRRC1 Number of Genes KLF6 ING3 PPP3CA PLXNB2 IPO11 CXCL14 SHCBP1 CCNI KRT6A ELOVL4 FAM46A RHOF ADAMTS1 ESRRG
G 480 400
320
240
160 Number of Proteins Proteins of Number 80
0
SP1 NFY TCF3MAZLEF1 JUN FOXO4 NFATC1AACTTT REPIN1 Key transcription factors
d Supplementary Figure 3
Group 1: 153 genes Group 2: 156 genes DOWN in Rat & UP in Axolotl UP in Rat & UP in Axolotl RUFY3 GNB5 SLC17A6 DKK3 GUCY1B3 KLHL7 CYP7B1 ATP6V1A NACC2 ZBTB1 TUBB3 REEP1 A Group 1 GO terms SERPINH1 LAMC1 GPNMB GPR34 SNX7 CALHM2 CNPY2 USP18 PLBD1 HADH MAN1C1 LEPROT B Group 2 GO terms RTN2 GNG13 ARL16 ARHGEF25 NXPE3 PRPH PCMT1 DST YPEL3 RGS5 TUBA8 STK39 LRRC8D COL3A1 SCPEP1 ATF1 PXDN C1QC PLGRKT HBP1 S100A4 SGCE TAGLN FN1
WDR47 CHGB TCEA2 ACSS3 FGF12 MIA3 ABHD3 KLC1 KIF5A MACROD1 UBE2E3 TMEM38A ALDH2 RBKS PDLIM7 ACTA2 COL12A1 TFPT CDK20 CPT1A GAMT PEPD QARS IGFBP5 extracellular matrix organization
PSIP1 FAM19A2 CCDC117 ASH1L SMARCA2 GJB6 UCHL1 NEXN KCNJ10 SNCB STMN3 ELAVL2 ZEB2 PTTG1IP ARSB TNFSF12 ABHD12 CCNG1 ARHGAP24 LUM CNOT6 GBA ARAP1 NPRL2 collagen fibril organization neuronal development ALDH5A1 SIRT5 OLFM3 SUSD4 CBLN1 MDGA2 RIC3 CHCHD6 PGBD5 STMN2 NEFM BMPER TLR2 NAT1 QSOX1 SEMA3D INMT PTPRO RARRES1 COL6A3 PSCA COL5A2 TP53I3 PTPLA developmental process cell migration AIFM3 SPOCK3 RUSC2 BTBD2 CCDC92 EPDR1 YPEL5 EML1 NIPSNAP1 OLFM1 ZMYM2 GPM6A TMEM37 LGALS9 C1QB PLIN2 PLAC9 DSCR3 COL6A1 IAH1 LGMN ANXA1 HMOX1 AP1S2 cellular component movement FXR2 CRISPLD2 NDRG1 CBX7 CDH11 COQ3 DPCD SPTB DNAJA1 GLRX2 PTGDS ARL6 C1R EEF1D RUFY1 XYLB NRP1 GDA XDH SEC22A COL4A1 COL4A2 LAMA4 DAB2 response to wounding PGM2L1 NLGN1 TENM3 EBF2 PPDPF NKIRAS1 CHN1 SLC13A3 GPRC5B PCDH18 HEY1 AK1 VIM DGAT2 AGTRAP TGFBR2 VPS13C LAMP2 VAT1 PRSS23 LITAF GLB1 TMEM86A PDCD11 cell adhesion BNIP3 DDC SATB1 SCRN1 REEP6 PVALB CHGA FAM110B MYH10 NDRG4 S1PR1 ALDH1A1 neuron projection STOM APRT NCBP2 ATOX1 ABCA1 TPM1 CTHRC1 COL1A1 LOXL2 RASSF4 THBS4 BTG1 intramembranous ossification GAS2 FAM189A2 CA2 FUT9 SSTR2 TOX DNAJC21 SLC24A2 DAO KLHL15 FKBP1B SH3BGR LMCD1 COL1A2 CTSK POSTN CLN5 STRA6 RBP1 POLD4 SLK TMEM176B HIST2H2BE COL5A1 vascular development SERPINI1 MEST CTPS2 RTN1 ROGDI LINGO1 CD59 MAP1B PFKM IGSF21 SPTBN1 CDH6 PAOX OLFML3 MAN1A1 SERPINF1 CSTB LGALS1 THBS2 MMP2 ORAI1 PTPN2 LRRFIP1 TNC cell motility 0 2 4 6 8
EPHA5 AGT RAB40B CDK14 MYH1 SLC7A10 CADM3 PTBP2 DCUN1D4 KCNAB1 NRCAM CHODL TYROBP EIF4A2 TRIM27 GGCX FYN F10 PSME4 CXCL12 GRN EIF1AD TXNDC17 IL10RA 0 5 10 12 14 16 18 20 22 10 15 20 25 30 35 40 45 50 55 LGI1 RUNDC3B DZIP1 FSD1L FAM32A ABCG2 CSPG5 PYGM ERMN N of genes in each term VAMP5 ICAM1 MCAM CRYZ COMMD7 FBN1 NID2 TPM3 AIF1 MRC1 PROS1 SERPING1 N of genes in each term AGT CSPG5 LUM LAMC1 COL5A1 FGF12 SMARCA2 ERMN COL4A2 Genes in GO terms: COL3A1 COL5A2 Genes in GO terms: BNIP3 CA2 MMP2 -Neuronal development COL12A1 -ECM organization NEFM LGI1 PXDN MAP1B COL4A1 TNC SERPINH1 -Vascular development STMN3 -Neuron projection NRCAM LAMA4 COL1A2 PVALB FN1 TUBB3 NRP1 OLFM3 POSTN TGFBR2 STMN2 COL1A1 KIF5A NLGN1 SNCB HEY1 HMOX1 RTN1 OLFM1
MDGA2 CBLN1
RUFY3 SLC7A10 FUT9 PCDH18 ALDH5A1 SERPINI1
Group 4: 228 genes Group 3: 77 genes UP in Rat & DOWN in Axolotl DOWN in Rat & DOWN in Axolotl C Group 3 GO terms RRAGC WAPAL TMEM209 ISG15 RAB27A SMC4 SMC2 ITGA6 MCM4 JUNB CERK FUCA1 BLNK NUSAP1 UTP14A D Group 4 GO terms SPRYD3 SNX10 PRKACA RAB27B PDE4D CMAS MAPK12 PELI2 SLFN13 UHRF1BP1 DDX39A MFSD11 TMEM181 UBE2C NUP160 NONO CNDP2 SFPQ PDLIM7 FLNA STK17B EHD4 ATAD2
ARRDC1 HNRNPAB MYC TRIB1 TTK DBNL TIMP1 HK2 EXT2 ATRX TMEM168 IRF7 MEX3C OCLN RBCK1 nucleic acid metabolism HABP4 NFYB CALB2 PPP3CA RHOF LNX1 ESRRG RIMKLB sterol biosynthesis IFITM3 TMEM208 SDF2L1 PLXNB2 SNRPA MRTO4 LGALS3BP HCLS1 PSCA KIF22 SEC14L1 PNLIP PTBP1 APAF1 PARP12 nitrogen compound metabolism cholesterol biosynthesis ATP2A2 TNK2 MRAS SUGP2 FAM103A1 MDP1 DST FBXW7 GADD45G FAM76B ARHGAP11A TMEM123 PRC1 DCTPP1 SNX18 CFD FBL KIF20A ST14 COL11A1 HIST1H1C RBM47 TGIF1 chromosome condensation lipid biosynthesis TDG NGFR GMPPA CANT1 CFP SLC35A3 SLC30A1 NCBP2 TIAL1 PARP9 HMBS NCAPH2 PARP14 CCDC43 RAE1 STRBP ELOVL6 SSBP2 SLC38A2 FAM98A CYP51A1 CHCHD10 MYH10 mitotic cell cycle isoprenoid biosynthesis TACC3 RAB5C LPCAT1 DAPP1 TRAM1 LIMA1 KDELR1 MYCL1 LMNB1 TOP2A RNF144B NABP1 SEC23B PELI1 ABCB4 cell cycle FAM110B TMEM50B MPP6 GPT2 ABCB9 ACOT7 STARD10 FAM84A PLK2 TPM3 GPR84 ZDHHC7 ZNFX1 EMP1 RPS6KA3 ARRB2 MDM2 MTPAP DDX54 RPL14 DNAJC3 VPS37B BCL10 cholesterol metabolic process DNA replication MX1 ETS1 NASP FEN1 RRM1 OTUD1 ACTN1 ALDH18A1 PMM2 DNASE1L1 TNIP1 CMKLR1 SHCBP1 AURKA KIAA0101 MIA3 NEK7 MFSD6 PTPN4 CHKA GHITM AQP4 TLCD1 macromolecule metabolism lipid metabolism PCNA NFIL3 IRF3 TMOD3 TNFRSF12A FAM3C PTCD3 MED11 ETF1 ENTPD2 AURKB CYFIP1 WHSC1 PFN1 LRRC59 DNA conformation change USP32 Sep-08 ITFG1 ALG2 SPTBN2 HMGCS1 SHISA4 TRIM16 cellular lipid metabolism DNAJB11 MCM2 MCM7 KLF6 RCOR1 ARL11 EIF2A TEAD1 MYOF SLC25A39 ANXA2 S100A10 PLIN3 FOS IL17RA ADCY4 RNF213 FOXO1 SLC35C1 PNP DAPK3 DSC2 CASP1 FAM107B MCM6 CELF2 ESM1 MGAT2 MPV17L2 MPZL1 nuclear division
SYT16 KIAA0664 ACLY NCOA7 MVK SLC30A9 FDPS PPTC7 coenzyme A metabolism TK1 CYB5R4 SDC1 MTA2 ANTXR2 CCNB1 CDK1 CIB1 GADD45A CENPF CHMP6 VPS36 CXCL10 SNRNP40 RGS2 response to stress 0 1 2 3 4 5 6 7 8 9 EPSTI1 PBK CDT1 HES1 MANF RRAS TFPI2 IQGAP1 ELAVL1 ADAMTS1 VASP IL1R1 AVPI1 SGK1 0 7 SACS PGP DYNC1LI2 SQLE AAED1 SLC7A1 HMGCR MSMO1 10 11 12 13 14 21 28 35 42 49 56 63 70 77 84
TSPO PDLIM2 FAM46A CCNB2 MFSD1 SURF4 IRF1 MAP2K3 ECT2 MIDN TARS SLC2A5 EIF2AK2 GLTP SLC31A1
ARHGEF4 CDS1 PLCXD2 DYNC1I1 MAL N of genes in each term N of genes in each term CCNA2 CBFB RACGAP1 CARS RPL14
NCBP2
ACOT7 ZNFX1 Genes in GO terms: SNRNP40 Genes in GO terms: CDS1 TARS MTPAP FDPS HMGCS1 -Sterol biosynthesis DNAJB11 CARS -Nucleic acid metabolism CELF2 TMEM123 ACLY SQLE FBL PTBP1 CMAS -Lipid metabolism -Cell cycle HMGCR DDX54 UTP14A ARRB2 ELAVL1 TK1 DNASE1L1 CYP51A1 SNRPA RRM1 CHKA ATRX CDT1 ELOVL6 APAF1 TOP2A SFPQ SMC4 MVK AVPI1 CBFB NONO FEN1 PRC1 PCNA AURKA HK2 PLCXD2 PBK SMC2 FOS CDK1 NFIL3 MYC AURKB UBE2CNUSAP1 CCNA2 RGS2 MDM2 CCNB1 ETS1 MCM2 MCM4 KIF22 IRF1 RACGAP1 JUNB GADD45A MCM6 CENPF TACC3 PLK2 CCNB2 IRF3 GADD45G MCM7 TTK NASP TDG RRAGC CIB1 Supplementary Figure 4
A 110 UPregulated genes/proteins C BIOLOGICAL PROCESS
RNASET2 TXNDC5 TPP1 CTSD DPP7 POR IQGAP1 HNRNPF TAGLN2 VGF (listed by BinGO p-value)
CAPG MYOF SNRPD2 MYO1C FABP4 CTSB LMNB1 NCAN ESYT1 PSMB10 extracellular matrix organization
PDIA6 P4HB FKBP10 COL3A1 S100A11 LAMP2 ANXA1 HIP1 CTSZ COPZ1 collagen fibril organization
ANXA3 HEBP1 CTSA CFH SFPQ NONO ITGB1 COL6A1 CALD1 ITGA6 peptide cross-linking extracellular structure organization DCN HNRNPAB SND1 H2AFY FLNA CORO7 FN1 ACTN1 PSMB9 LIMA1 collagen biosynthetic process TMED10 SERPINH1 RCN1 CLIC1 PDIA4 HMGCL COL4A2 COL4A1 RCN3 VIM cellular component organization LUM LCP1 NPC2 APOE SYNCRIP ARSB ANXA2 ERP29 COL1A1 AIF1 vacuole organization
ACP2 TGM2 CAPRIN1 NES TLN1 PTBP1 MSN PCOLCE UAP1L1 PTPN6 actin filament bundle assembly
RRBP1 LGALS3BP SF3A3 STAT1 LGALS3 PSAP DNAJB11 CORO1C HNRNPA3 HK2 cellular process cellular component assembly CP PNP DDOST ASAH1 PRDX4 CTSH PEPD TPM4 EIF4A3 COL1A2
0 SF3B3 MVP ARPC1B MX2 CALU PDLIM4 SCPEP1 NAAA GLB1 GM2A 10 20 30 40 50 60 70 80 Number of Proteins
B 90 DOWNregulated genes/proteins D BIOLOGICAL PROCESS AQP4 MOBP GNAI1 MAPRE3 CADM3 FGF1 NCDN PYGB AK1 (listed by BinGO p-value)
SLC1A2 TAGLN3 SNCB BCAT1 MPP6 PFKM ATP1B1 PVALB ATP1A2 small molecule metabolic process
ALDOC CPNE6 TUBB4A TUBA4A PCMT1 MAPT SUCLA2 MVK ATP1A3 alcohol metabolic process small molecule catabolic process STX1B MDH1 GNAO1 AUH ACLY GDI1 ME1 FDPS ALDH1A1 glucose metabolic process FBXO2 PPM1F HMGCS1 MYH10 GOT1 SPTBN1 AK4 SNCA HSPA12A primary metabolic process
CADPS PREPL LDHB THY1 MAP6 MAP2 TTC1 LANCL2 CA2 catabolic process dicarboxylic acid metabolic process PPME1 PANK4 SCRN1 AAK1 IMPACT UBE2O RNF14 CPLX1 FASN carboxylic acid metabolic process CUL3 PLCL1 UBE2K VSNL1 ACSS2 NDRG1 PAK1 PAK3 ACOT7 oxoacid metabolic process
ALDH5A1 UCHL1 HPCA CALB2 RUFY3 CPLX2 UBE2V2 TUBB3 NPEPPS organic acid metabolic process
PDXP SEC14L2 SCG2 ABAT SH3GLB2 PYGM RAP1GAP SIRT5 ACSL1 0 10 20 30 40 50 Number of Proteins Supplementary Figure 5 T10 12 weeks post-SCI T10 Intact – no injury Supplementary Figure 6
T10 2 weeks post-SCI T10 Intact – no injury A CD45 C CD45 CD34 CD34
B CD45 D CD45 CD34 CD34 Supplementary Figure 7
PDGFRB *** 6.0
Ct 4.5
ΔΔ 3.0
RQ 1.5 0.0 Intact Injured