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Yan Et Al. Supplementary Material SUPPLEMENTARY MATERIAL FOR: CELL ATLAS OF THE HUMAN FOVEA AND PERIPHERAL RETINA Wenjun Yan*, Yi-Rong Peng*, Tavé van Zyl*, Aviv Regev, Karthik Shekhar, Dejan Juric, and Joshua R, Sanes^ *Co-First authors ^Author for correspondence, [email protected] Figure S1 tSNE visualization showing contributions to cell types by batch for photoreceptors (a), horizontal cells (b), bipolar cells (c), amacrine cells (d), retinal ganglion cells (e) and non-neuronal cells (f). Each dot represents one cell. Colors distinguish retina samples. Source of each sample is shown in Table S1. Overall, batch eFFects were minimal. Figure S2 Violin and superimposed box plots showing expression of OPN4 in RGC clusters Figure S3 Heat maps showing expression patterns of disease genes by cell classes in the Fovea and periphery. Only genes expressed by more than 20% of cells in any individual class in either Fovea or peripheral cells are plotted. Table S1 Information on donors from whom retinal cells were obtained for scRNA-seq proFiling. Table S2 Publications reporting single cell or single nucleus profiling on cells from human retina. 1 Figure S1 a b c PR HC BP H1 H2F1 H2F2 H3 tSNE1 tSNE1 H4 tSNE1 H5 H9 H11 tSNE2 tSNE2 tSNE2 e AC f RGC g Non-neuronal tSNE1 tSNE1 tSNE1 tSNE2 tSNE2 tSNE2 Figure S2 OPN4 4 2 log Expression 0 MG-ON MG-OFF PG-OFF PG-ON hRGC5 hRGC6 hRGC7 hRGC8 hRGC9 hRGC10 hRGC11 hRGC12 Figure S3 Fovea Fovea Peripheral Peripheral Rods Cones BP HC AC RGC Muller Astro MicG Endo Rods Cones BP HC AC RGC Muller Astro MicG Endo ARL13B MAPK8IP3 EXOC6 LSM4 Expression SLC24A1 LRIF1 Strength SAMD11 KREMEN1 SAG KBTBD7 2 RP1 ISCU ROM1 ICA1 1 RHO IBTK RGS9 HS3ST1 REEP6 HIVEP3 0 RDH12 HDLBP RBP3 H1F0 −1 PRPH2 GTF2B PRCD FYN PDE6G FKBPL PDE6B FKBP9 PDE6A FEZ2 NRL FERMT2 NR2E3 FER MAK FAM213A IMPG1 EXOSC10 GNAT1 EGLN3 FAM161A EFHC1 EYS DLC1 DMD CWC25 CRB1 CRK CNGB1 COL6A1 CNGA1 CDO1 CABP4 CAPZA1 AIPL1 CAMTA2 ABCA4 C4orf32 TMEM136 C11orf49 NEURL1 BRE USH2A BRD3 UNC119 BRAP RPGRIP1 BCAS3 RAX2 AURKAIP1 PROM1 ATP13A2 NEUROD1 ATG12 KCNV2 AFF3 CACNA1F ABCA6 MEF2C MT−ND4 THBS4 NFE2L2 PRTG PDE4DIP C9orf135 RPL24 NXNL1 C1GALT1C1 VTN TRIP12 MMP9 SMARCA2 DPF3 SRD5A3 TULP1 KIF21A RS1 TUBB3 RP1L1 SPG7 RGS9BP POLG RD3 NDUFS1 PLA2G5 MTPAP PDE6H CISD2 PDE6C AUH OPN1LW IFT43 IMPG2 TTC28 GUCA1A GRN GNB3 KCTD7 GNAT2 CLN8 CRX CLN6 CNGB3 CLN5 CDHR1 TPP1 CC2D2A PPT1 GAS7 IKBKG FAM84B WDR34 OPN1MW TMEM231 GUCA1B CEP41 IGF1 PDE6D IGSF21 OPTN THSD7A PAX6 TRPM1 GPR143 GRM6 TMEM67 FAM46A PEX6 SERPINI1 PEX5 OTX2 PEX19 TNR PEX16 HTRA1 PEX14 ST3GAL1 PEX10 PCSK5 IFT80 TSEN54 GNB1 KCNK1 ZFP82 HMX1 UTRN COL9A1 UCHL3 TFAP2B UBXN2A LINC00461 TBC1D5 GBAS TBC1D4 TMEM161B STAT2 PHGDH SLK GCSH SLC16A7 PSPH SEC11C ZNF891 RBFOX1 ZNF652 POP4 WDR5 OSCP1 WBP4 NRXN3 WAC NNT VKORC1L1 MYT1L UMAD1 MYSM1 UBIAD1 MRPS15 UBE2L3 MRPL19 TRMT61B MPRIP TRAPPC3 INSR TRAF3IP1 INPP4B TLL1 HS6ST3 TES GPR158 TANGO2 GPATCH2 SYT13 FAXC SYNJ2 COMMD6 SUPT3H COMMD1 STAG1 CEP162 ST7L AKT3 SPTSSA AGAP1 SPTBN1 ZNF280D SPCS3 VPS13C SMIM12 TXNRD2 SMG6 TSC22D2 SLC25A22 TMEM181 SIX3 TMCO1 SH3PXD2A SLC6A15 SEL1L SIX6 SCFD2 PRKAG2 SCAMP1 PNPT1 RPLP2 NEAT1 RPA3 MGAT5 RORA MEIS1 RELN MADD RALGPS1 LSM8 RALB LRP12 PTCD2 LPP PSMC3 LMO4 PRRT1 GNB1L PPP2R3A GMDS POU6F2 FBXO32 PNPLA2 FARS2 PKN2 FAM120B PKIA EXOC2 PCLO DST PCBP3 CADM2 OXR1 CACNA2D1 OXA1L CACNA1A ODF2L BNIP1 NUP160 ATXN2 NUDT7 ARHGEF12 NSF ANKH NR1H3 NDUFAF6 UQCRFS1 MVB12B TSN MTOR TRAPPC9 MOCS2 TOMM40 MGMT TMEM97 MFF TLE4 METTL15 TDRP ME3 SYN3 MCPH1 SV2C STOX2 Figure S3-2 Fovea Fovea Peripheral Peripheral Rods Cones BP HC AC RGC Muller Astro MicG Endo Rods Cones BP HC AC RGC Muller Astro MicG Endo STK19 ACBD5 SRPK2 ABHD12 SPEF2 ABCC6 SNX7 CNTFR SLC16A8 TRIOBP RORB ST7 PVRL2 SPRED2 POLR2B SOX11 2 PLEKHA1 SLC44A1 PLA2G12A SEPT9 PHACTR3 SEC14L1 1 PCF11 RXRA PCDH9 P4HA2 0 PBX2 MEIS2 NT5DC1 KALRN −1 NPLOC4 ISOC1 NOTCH4 HACE1 NELFE GRIK4 NDUFC2 GLCCI1 MRPL14 GAB2 MARK4 FOXP1 LSM14A ETV1 KRAS DSEL KMT2E DGKG KCNJ3 BTBD3 IGFBP6 BANP HSF2 BAMBI HERPUD1 ARHGAP20 HERC1 ANAPC1 GPX4 ALCAM FAM110B AKAP13 EXOC5 ADGRB2 ERICH1 HDAC4 EIF3A NR1D1 EFCAB14 FBXO41 DXO CHN1 DAPK3 IFT88 CD63 TTC21B CCSER2 VPS13B C9orf91 VSTM2B B3GLCT DPP10 ATP6V0D1 CREB5 ATF7IP2 CPM ATF6B ARHGAP22 ARHGAP21 TMEM263 ACAD10 MPP7 ABHD2 DGKD ZNF513 CTTNBP2 WDPCP AFAP1 TUBGCP4 ZBTB41 TUB VEGFA TTLL5 TRPM3 TTC8 TGFBR1 TRNT1 SOD2 TRIM32 SKIV2L TOPORS RAB30 TMEM126A MBP TIMM8A LYAR SPATA7 LHFP SNRNP200 KHDRBS3 SLC7A14 KCNMA1 SLC25A46 FOXK1 SDCCAG8 CNTN4 RTN4IP1 CDH6 RPGRIP1L CD46 RPGR BCAR1 RP9 ADCY5 RDH11 ZNF423 RCBTB1 WFS1 RB1 WDR19 RAB28 TMEM237 PRPS1 RIMS1 PRPF31 NR2F1 PRPF8 NPHP3 PRPF6 IFT172 PRPF4 CNNM4 PRPF3 ARL6 POMGNT1 ADAM9 PNPLA6 TRDN PHYH TGFB2 PGK1 TCF7L2 PEX7 COL24A1 PEX2 PEX1 TCF4 PDZD7 GOLIM4 PCYT1A PLCE1 PANK2 CYP26A1 PAF1 CAV1 OPA3 DDR1 OPA1 COL4A3 OFD1 APOE OAT RLBP1 NBAS RGR MVK MTTP MT−ATP6 EFEMP1 MKKS CLRN1 MFN2 CDH23 LZTFL1 LUM LCA5 TRIB2 KLHL7 CFI KIZ USH1C ITM2B KCNJ13 IQCB1 ESPN INPP5E CDH11 IMPDH1 PAX2 IFT81 NPHP4 IFT27 NDP IDH3B SLC1A3 HK1 HGF HGSNAT ARID5B HARS FMNL2 GNPTG CDKN1A GAR1 GJA1 FLVCR1 TMEM119 EXOSC2 SPI1 EMC1 HLA−DRB1 ELOVL4 HLA−DQA1 DRAM2 PLXDC2 DHX38 IRF8 DHDDS PILRAC3 CTNNA1 PTPN1 CSPP1 ETS2 CLUAP1 KLF6 CLN3 PRSS23 CLCC1 MYOF CIB2 MECOM CHM EMCN CEP290 DAAM2 CEP250 ANGPT2 CEP164 SASH1 CEP78 CYP1B1 CEP19 GRAMD3 CCT2 PDE7B C21orf2 FOXC1 C12orf65 REST BEST1 IGFBP7 BBS12 FILIP1L BBS10 CD34 BBS9 TIMP3 BBS7 SPARC BBS4 JAG1 BBS2 CFH BBIP1 TRAM2 ATXN7 TRAF3IP2 ATF6 TNS1 ASRGL1 KANK2 ARSG FOXO1 ARL2BP FNDC3B ARL3 ETS1 ALMS1 COL6A2 AHR COL4A1 AHI1 CCNL1 AGBL5 CAV2 AFG3L2 LIF ADIPOR1 INHBB ACO2 ADAMTS9 Table S1 Donor Donor Duration to process Donor ID Retina ID Age sex COD after death (hour) 10X Kit H1 H1 74 Male Lung Cancer 6 V2 H2 H2R1 78 Male Metastatic Melanoma to brain 14 V2 H2 H2R2 78 Male Metastatic Melanoma to brain 14 V2 Left tonsillar squamous cell carcinoma metastatic to H3 H3 60 Male brain and left orbit 6.5 V2 Diffuse B cell lymphoma spread to thorax and epigas- H4 H4 64 Male trum 5 V2 H5 H5 53 Female Interstitial Lung Disease 5 V2 H9 H9 76 Male Metastatic Melanoma 6.5 V3 H11 H11 65 Male Metastatic Melanoma 3 V3 Table S2 Reference Platform Age #Donors # cells Separate fovea/ # clusters Identify Cells or nuclei macula and types within periphery classes 12Peng et al., 2019 10X, V2 Adult 1 2,383 No 9 Yes cells 56Hu et al., 2019 Modified Fetal week 19 embryos 2,421 No 21 No cells STRT 5-24 weeks 55Lukowski et al.,2019 10X, V2 Adult 3 20,009 No 17 Yes cells 59Voigt et al., 2019 10X, V3 Adult 3 8,217 Yes 17 Yes cryopreserved cells 58Menon et al., 2019 10X, V3 and Adult 6 23,432 Yes 9 No cells Seq-Well 57Liang et al., 2019 ICELL8 Adult 3 5,873 Yes 7 No nuclei 60Sridhar et al., 2020 10X,V1,V2,V3 Fetal 4 embryos 61,164 Yes 10 No Cells This study 10X, V2 and Adult 8 85,000 Yes 58 Yes cells V3.
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