Supplementary Information Supplementary Figure 1 2 Supplementary Figure 2 3 Supplementary Figure 3 4 Supplementary Figure 4 5 Supplementary Figure 5 6 Supplementary Figure 6 7 Supplementary Figure 7 8 Supplementary Table 1 9 Supplementary Table 2 23 Supplementary Table 3 25 Supplementary References 26

1 Supplementary Figure 1

Supplementary Figure 1. Testing -specific dataset by differential expression analysis and known marker for transcriptions. (A) Differential analysis of spermatogenesis dataset provided by Xia B., et al. (2020) shows unique expression sets among individual cell stages defined by binary logarithmic Fold Change (log2FC) of gene expression at a threshold of 0.25. (B) PCA-based trajectory analysis is consistent with gene sets for cell-stage identifications as reported in human single-cell atlas (Guo et al., 2018). List of gene marker clusters in individual stages is provided in Supplementary Table 1. (C,D,E) Normalized

2 absolute spermatogenesis transcriptome shows total cellular gene , mitochondrial gene transcription, and RNF20 expression known for TCEA inhibition. [all statistical analysis provided in the figure was tested by Pearson’s correlation at a cut-off p-value < 0.001]

Supplementary Figure 2

Supplementary Figure 2. TCEA expression profile in human embryogenesis. (A,B) TCEA expression profile of human embryogenesis classified by days [day 3-7] (left) and tissue types [epiblast, not applicable, primitive , and trophectoderm] (right) provided by (Sladitschek et al., 2020). (C,D) Correlation analyses between embryogene-related gene transcription and TCEA1 (left) and TCEA2 (right). [all statistical analysis provided in the figure was tested by Pearson’s correlation at a cut-off p-value < 0.001]

3 Supplementary Figure 3

Supplementary Figure 3. (GO) analysis of genes highly regulated by regulons involved in RNAPII-mediated gene transcription in Sc-4, RS-1 to RS-4 and ES-1 to ES-4. Each abbreviation provided in the figure is Sc = Spermatocyte; RS = Round spermatid; ES = Elongating spermatid from individual developmental stage. [gene ontology (GO) analyses were tested by Fisher's exact test with a cut-off p-value = 0.01]

4 Supplementary Figure 4

Supplementary Figure 4. Expression profiles of genes involved in transcription-coupled nuclear excision repair and correlation analyses of TCEA cotranscriptionally expressed during DNA repair pathways. (A,B,C,D) absolute expression profiles of genes involved in TC-NER in individual spermatogenesis-related cell-stages (POLR2A, XPC, ERCC6, and ERCC8, respectively). (E,F) Correlation analysis of DNA repair pathway expressions with TCEA1 and TCEA2. DNA repair pathway abbreviation: BER = , MMR = Mismatch repair, HR = , NHEJ = Non-homologous end joining, and ICL = Inter-crosslinking repair. [all statistical analysis provided in the figure was tested by Pearson’s correlation at a cut-off p-value < 0.001]

5 Supplementary Figure 5

Supplementary Figure 5. DNA repair pathway expressions in Principal component analysis trajectories in cell-type specific spermatogenesis. Each of the DNA repairs show high expression in the early stage of Spermatogonia (Sg) during the transcriptional bursting. NHEJ also shows high expression in Round spermatid (RS) stage, and ICL shows high expression in Spermatocyte (Sc) stage as they are responsible for double strand break (DSB) repair in G2/M-phase and S-phase of , respectively as we observed in Supplementary Figure 5. Color represents expression level from high (purple) to low (grey). DNA repair pathway abbreviation: BER = Base excision repair, MMR = Mismatch repair, HR = Homologous recombination, NHEJ = Non-homologous end joining, and ICL = Inter-crosslinking repair. List of genes involved in the DNA repair pathways is provided in the Supplementary Table 2.

6 Supplementary Figure 6

Supplementary Figure 6. Correlation analyses of DNA repair pathway expression with activity defined during the transcriptional bursting (A) and the post bursting (B). DNA repair pathway abbreviation: BER = Base excision repair, MMR = Mismatch repair, HR = Homologous recombination, NHEJ = Non-homologous end joining, and ICL = Inter-crosslinking repair. [all statistical analysis provided in the figure was tested by Pearson’s correlation at a cut-off p-value < 0.001]

7 Supplementary Figure 7

Supplementary Figure 7. Gene expressions for determining Cell cycle in S- and G2/M-phase during spermatogenesis. Relative expressions of S-phase (left) and G2/M-phase (right) in the cell cycle of individual cell-type spermatogenesis in human.

8 Supplementary Table 1

Table 1. Curated lists of differentially expressed genes in each stage during human spermatogenesis compared with the curated list of stage-defining genes from Human Atlas.

Cell stage Gene name Gename from Human Atlas

Spermatogonia (Sg-1) "UTF1","C19orf84","BEND4", "MAGEA4", "DAZL", "SYCP3", "FGFR3","LIN7B","MAGEB2", "DMRT1", "DMRTB1", "THRA","MAGEA4","NEIL2","M "SOHLH1", "CHEK1" FHAS1","PAFAH1B3","RGMA", "CDK17","SOX4","HMGA1", "LMO4","TCF3","SNAPC2", "COTL1","SMS","KCNQ2", "TLE1","STK24","DUSP5", "GRN","RFWD3","PIWIL2", "PPP2R1A","LCOR","IRF2BPL" "DAB2IP","CPEB1","USP31" , "ELAVL2","PAFAH1B2","USP11", "DCAF4L1","PHF13", "KMT2B", "TMEM123" , "PABPC4", "PARP1", "CCNI", "POLR2A", "RPSA" , "YWHAB" , "TOMM34", "GATAD2A", "RNPS1", "CELF1", "RPS12" , "RYK" , "RPS19" , "MTPN","MAP4K4" , "TUBA1B", "BANF1", "CBL", "HNRNPDL", "HSP90AB1", "STRN4" , "BCCIP" , "ZNF428" , "ALKBH5", "DYRK1A" , "TKTL1", "RPS5", "CDK2AP1" , "COX7A2L", "CCDC117", "JARID2", "TDRD1","RPLP0", "TRMT112", "CD164", "PHF8", "PDIA4", "NR6A1" , "RPL18A", "RPS21", "PTPA" , "SUMO3", "RAC1" , "RPL38" ,

9 "TUBB" , "EEF1B2" , "CBX3", "SPTAN1", "DNAJB6", "BSG", "RPS16", "RPS2" , "RPL18", "RACK1" , "RPS28" , "PFN1"

Spermatogonia (Sg-2) "CT45A6" ,"PNMA5", "SSX3","CT45A10","SSX2","SSX 2B", "CT45A9","RHOXF2" , "ZNF280C" , "MCM2","","MCM6","RHO XF2B","MAGEA4", "CTCFL", "PAFAH1B3","UNG", "HMGA1", "MYBL2", "MCM5","TRMT6", "TLE1","GINS2", "NAE1", "BTG3","TKTL1", "DAZ2","SRM", "DAZ3","DAZ1","PDIA6", "APLP2", "PDIA4", "SLBP","HERC5", "VCX", "CCT6A", "DPEP3", "DMRT1", "NUP93", "XPO1","VCY", "NUDT3", "DAZ4","CENPH", "PRAME", "RNPS1", "ARCN1", "POLR2A", "TSPYL2", "HIST1H4C" "CALR","NOMO2", "DDB1","NFATC2IP" "USP31", "YWHAE", "NASP","ANP32B", "SNRPB","SMC3","RIF1","NOM O3", "NOMO1", "MAP4K4", "PRKDC", "BSG", "PARP1", "RBPJ","CIRBP", "SUZ12", "NCL", "TRMT112","HMGB1", "UBA2","DMRTB1", "SMC1B", "PFN1","HNRNPD","HNRNPD L","MTRNR2L1" "BUD23", "CNOT7", "HSPA5", "PTMA", "HSP90AB1","PABPC4", "MTRNR2L12","MTRNR2L8"

10 Spermatocyte (Sc-1) "MAGEA9", "TEX19", "DAZL", "DMRTB1", "SYCP3", "PNMA6E", "JADE3", "SPO11", "MLH3", "DDX4", "MAGEA9B","BEND2", "BRCA1", "DMC1", "SYCP1", "KIF1A", "MAGEC2", "SPAG6", "ZPBP2" "CLSPN", "CDC6","CTCFL", "ZNF280C","HELLS", "PRIM1", "DPH7","C18orf63" "CCDC73", "CHAF1A", "RAD51AP2" "PRSS50", "VCX3B","DAZ2","DAZ1","GIN S2", "TRAFD1", "VCY", "MEIOB", "DAZ3","BTG3","VCY1B", "IQCB1", "VCX", "HIF1A", "ZC3H13", "DAZ4","YTHDF1", "BCAP31", "NPTX2", "VCX3A", "PSMD1", "DPEP3", "SCML1", "TAOK3", "SYCP3", "VCX2","TOP2B", "SAE1","ZCWPW1", "ANKRD31","HIST1H4C" "TEX101", "POLE","TOP2A", "CENPH", "SMC1B", "SFR1", "SMC3","NASP","BUD23", "ABCA5", "PPIG","ACBD3", "HERC5", "CBX1", "SDF2L1","KNL1","HIST1H2BA" "DUT", "SMCHD1", "TSPYL2", "HDAC6", "SUZ12", "BOD1L1", "TKTL1", "ARIH2", "GOLGA2","HORMAD1","NCL ", "APLP2", "DNAJC1", "USP9X", "HIST1H2AA" "WEE1","RIF1","PRPF8", "RRM1","U2SURP", "DDX24", "NIPBL", "HMGB1", "DAZL","EIF5B", "SYCP2", "STAG3","SYCP1", "MTRNR2L1", "MTRNR2L12","MTRNR2L8"

Spermatocyte (Sc-2) "LY6K", "C18orf63",

11 "PLEKHG4","DMRTC2", "CCDC172","TRAFD1", "CDCA8", "MEIOB","MDC1", "ANKRD31","ART3", "PIP5K1A","IQCB1","PAN2", "CNTROB", "TEX101", "TEX14","TPTE2","MTF2", "CTSL", "HIST1H2BA" "TPTE", "CCP110", "BUB1", "TOP2B","HORMAD1","NUF2", "SLC25A31","C5orf47","SYCP3" ,"S100PBP","RCN2","PIWIL2","T OP2A","ARIH2","C5orf58","PR C1", "DAZL", "TERF2IP","HMGB2","ARL6IP1", "SYCP1","HNRNPA3","PNISR"," TDRD9","SUGP2","TDRD1","N BPF1","DZIP3", "SMC4", "HENMT1", "HSP90B1","SPINT2", "SETX", "KHDRBS1","PRSS21", "TMEM147","SNRPB","HIST1H4 C","HSPA2","SENP1","SMC1B","I LF3","BUD23","HNRNPA2B1"," SFPQ","LARP1","KDM5B","NBP F3","AC240274.1","RBBP4","PTP A","HNRNPM","HNRNPH3","C CT3", "ILF2", "SRSF11", "VAMP2","MLLT10", "SGO2", "CALM2","SMC3", "CBX3", "KNL1", "KIF5B","CIRBP","NIPBL","HSP9 0AA1","HIST1H2AA", "HSPA5", "SPATA8"

Spermatocyte (Sc-3) "C9orf57","C4orf46","SLC25A3 1","SPRTN","TM2D1","CNTRO B", "FKBP6", "HIST1H2AA","HIST1H2BA","C KS2", "TERB2","PLK2", "TEX14","CCDC112", "CCP110",

12 "CETN3","SLC2A14","FAM174A ","PDRG1","TFDP1","COMMD4 ","PIWIL1","HSPA2","TDRD1"," CTSL", "SLC2A3", "NUF2", "LRRC23","RCN2", "MTX2", "MGAT4D", "SYNGR4", "AC024940.1" "TMEM99", "TYMS", "C5orf58","SELENOS","H2AFZ", "PSENEN", "SPATA8", "SAC3D1", "RFX4", "NT5C3B", "DPY19L2","SPDYA","ZNRF2","S PINT2", "TPTE", "BCAP29", "DYNC2H1","SSNA1","MLLT10" , "TERF2IP","TESMIN", "ADAM2","RALGPS2", "ZWILCH", "SENP1","STK31","HMGB2","C ALM2","ZMYND10","SETX", "UBN1", "PNISR","ANKRD36C", "EIF5AL1","SNX14","FAM216A", "ANKRD36B", "C15orf48", "KPNB1","ANKRD36","ARL6IP1 ","KDM5B","HENMT1", "MORF4L1", "SAYSD1", "RBBP4","SUGP2","HORMAD1" ,"KRBOX1", "TUBA3D", "PRSS21", "SBNO1","SPAG6","TPR","NBPF 3","AC240274.1" "LYAR", "SPATA22", "NBPF1","TMEM225B", "TUBA3C", "DAZL", "TUBA3E", "SPINK2", "REXO5"

Spermatocyte (Sc-4) "C1orf94","TMPRSS12" "ISOC2","RGCC", "KRT72","GULP1","ADAM2","C

13 HST13", "ZBTB32", "AURKA","CCDC86", "CEP55","WDR63","ASH2L","PL A2G6", "ALKAL2", "ZC2HC1C","TBP", "TKTL2","CLGN", "SLC2A5", "CIAPIN1","GLB1L","CCNA1"," TUSC1","C21orf59" "NEK2", "CAVIN3", "C16orf71" "ZPBP2","DAW1", "TYMS", "CCDC42", "LZTFL1", "PCID2","TBPL1", "PPP3R2", "RAE1", "MRPL43", "KPNA5","INO80C", "NUP188", "TCFL5","SNW1", "HSF5","MRPL34", "PBK","REXO5","SPINK2", "MKRN1","ANKLE2", "LYAR", "TDRD7","SNRPC", "PCDH17", "RAN","AHCTF1", "SFMBT1", "COPRS","ASRGL1", "NDUFAF3","ZNF689", "IFT74", "C1orf56","AKAP12", "PTTG1","PPP1R2", "CCNB2","LDHC", "APH1B","TTK","TMEM225B" "WDR87","PLK1", "KDM4D","FBXO25", "SPATA22","FAM216A","KRBOX 1", "ELP5", "CETN1", "ETFRF1", "SPAG6","TYSND1", "ANKRD7", "SMARCA2","C15orf48" "DBF4", "GTF2A2", "CCT6B", "ATP6V1B2" "SPATA16","TUBA3C", "GYG1", "SLC26A8","ZMYND10","SPATA 8", "RFX4", "CENPF", "CCDC110"

Round spermatid (RS-1) "CTAGE8", "CTAGE4", "ZPBP","DDX4", "CTAGE1", "RGCC", "CDK7", "SPAG6","ZPBP2", "DNAH6",

14 "CDKL2","ISOC2", "CAMK4", "CREM" "WDR63","CEP55","CHST13", "EFHB", "AURKA","NAA20","NBPF11", "CCNB2","NBPF10", "GALNT3", "DNAL4","NBPF19", "C15orf61", "LRRC34", "NBPF12", "NBPF15", "KPNA5","PLK1", "NBPF14", "TTK","CENPF", "CCDC146","PABPC1", "CCDC42","NBPF9","CCDC11 0","CCDC83", "FBXO25", "MNS1", "HSF5", "NBPF20", "ETFRF1", "C11orf63", "SLC26A8","TBPL1", "PBK","PSMG1","SPATA16","DB F4", "PABPC3", "SNRPC","KRT10", "SMARCA2","WDR87","PTTG1 ","CAVIN3", "KDM4D","PPP3CC", "TKTL2", "GTF2A2", "HDGFL1", "CCNA1","AC240274.1" "BRD8", "SHCBP1L","ANKRD7", "NBPF3","ZPBP2","CCDC34", "SPAG6","CCDC62", "CLGN", "DYNLT1", "NBPF1","PRRC2C", "DNAJC21","CETN1","IFT74","L DHC", "MRPL34", "ANKLE2", "MRPL43", "LCA5L","SCCPDH", "NEK2", "LYAR", "C16orf71", "CCT6B","TMEM225B", "FMC1", "AKAP12", "REXO5","SPINK2", "CCDC173", "ELP5", "PPP3R2",

15 "COPRS","CNTRL","SPATA22"," APH1B","FSIP2", "TUBA3C", "ZPBP"

Round spermatid (RS-2) "C11orf53", "LRRC39", "FAM24A", "LRRC3B", "ENPP2","TMEM243","CCDC81 ","ODF3L1","OLFML2B","CFAP1 26","NUTM1","C4orf17","HIPK4 ","C1orf87", "SOS1", "C11orf97","DEUP1","C4orf47", "CCER1","GOLGA6L2", "CCDC146", "DYNC2LI1", "C1orf105", "LRRIQ3", "EFHB", "ZNF85","USP44","MNS1", "LINC00694","CFAP77", "SSMEM1", "GALNT3", "SPEF2","ADGB", "SPART", "C9orf116", "PPIL6","WDR78","PABPC1", "NBPF15", "NBPF12", "C11orf63", "NBPF10", "ALS2CR12", "NBPF14", "CCDC34", "NBPF20", "C1orf158", "SWT1", "CFAP206","TSSK4","NBPF11", "ZCRB1","DNAL4","CCDC89", "CCDC62", "REEP5","CCNB2","MAATS1", "HIST2H2AA4" "SH3GLB1","CTNNA2", "TBPL1", "ETFRF1","LCA5L","HMGN1"," CCDC173","CCDC110","PPP3 CC","HIST2H2AA3""DNAJC21" ,"OSCP1","SCCPDH", "PLK1", "PABPC3", "KDELR2", "NAA20","SLC26A8","PBK","GK AP1","C6orf10","ZPBP", "TRIM13","GTF2A2","PPP1R2P3 ","PSMG1","CCDC42", "FMC1",

16 "C7orf61","HSF5", "DBF4","SHCBP1L","FSIP2","LD HC","CCT6B","CETN1","REXO 5","ANKRD7","APH1B","LYZL2"

Round spermatid (RS-3) "LRRC3B", "FAM24A", "TPRG1","C4orf17","TJP3","TM EM262","C17orf98", "ODF3L1", "CATSPER1", "C4orf47","EQTN","IGSF10", "C6orf10","PLCH1", "PRSS55","CENPW","CLDN12", "GOLGA6L2","TSSK4","FAIM2", "C1orf105","LYZL4","FAM186A" ,"FAM205A","HIST2H2AA4" "NLRP1","LYZL1","LYZL6", "LYZL2","HIST2H2AA3" "GOLGA6D","SPACA1", "TMEM108","MAP7","SSMEM1", "ATP6V1E2", "MRPL39", "STAT4","LINC00694","ZMYND 15","FAM153A","FTMT", "CTNNA2", "GOLGA6A","CCDC82", "POLR1B","SPART","CNTN4"," C7orf61","RTKN2","USP44","AF G1L","HMGN1","CCER1","SUN 3","MAATS1","DUSP13", "C17orf50", "SNAP29", "RNF148","CCDC89","TFDP2"," ACTRT3","FAM153B","DIAPH3" ,"TTLL7","SETD9","TPP2","TEX 51","OLAH","ACRV1","SVIP","L RCH4","OSCP1","CFAP206","SP ATA46","C2orf16", "FNDC11", "FSIP2","CDKN3","WDR78","C CDC173","CCDC146","KLF5", "ZBTB20", "ZC3H14", "C1orf158", "SPACA3", "CXXC5","BRDT","SPACA4", "MNS1","EIF5B","SPACA7", "CCDC110","PSMG1","FAM209

17 B","FAM209A", "CCDC62", "ACTL7B"

Round spermatid (RS-4) "CA9","SPACA1", "OLAH", "LRRC52", "SUN5", "EQTN", "CCDC27","TJP3", "FAM205A","RNF148", "CD46", "MAN1A1", "PLCH1","TSSK4", "CD55", "TMC7", "SPACA4", "CRLS1","ACTRT3", "SPAM1","TEX29", "TRIM17","C1orf185","MS4A6E" ,"KLF5","SLC35A5","LATS2","FT MT","SCOC", "FAM153B","ERICH2", "ETNK1","FNDC11", "NDUFB6","LYZL6","C6orf10"," SPACA3","LPGAT1","TMEM270" ,"FAM153A","SETD9","BBX","C 11orf65","TFDP2","ACRV1","PR R30","ZBTB38", "DGAT2","POLB", "TXNDC2","SAXO1","LYZL2"," MEX3C","HINT3","RETREG1"," ZC3H14", "FAM209B","SLC38A9","FAM20 9A","SUN3","C2orf40","TES","D YRK4","LYZL1","SESN3","CCD C168","CALCOCO2","ASB17"," ADAM29","LRRC37A2","TEX33 ","CCDC89","SSMEM1","NDRG 3","C2orf42","CPEB2","C20orf1 73","LYZL4","LRRC37A","HIST2 H2AA3","SPATA46","SOX30","C CIN","ACTL7B","HIST2H2AA4" "PRSS55","SERP2","ERGIC2","TE KT5","C7orf61","G2E3","ZBTB2 0","CXXC5","C8orf88","IZUMO 2","SCP2D1","TP53TG5","ZNRF 4","CDKN3","AKAP3"

Elongating spermatid (ES-1) "SLPI","CCDC185", "IQCF6", "TNP1", "PRM2", "MYO1D",

18 "PRSS58","GATA6", "TNP1", "HOOK1", "SPATA12", "DCDC2C","PRSS37","DNAJB7" "SPATA18" , "C10orf120" "TP53TG5", "FAM71A","CCIN","KCNV2", "SRRM5", "CCDC168", "TXNDC2","TEKT5","FAM71B", "FAM57A","CD55","ACTL7B","P CCB","TTLL2", "LTN1", "PCMT1", "FAM209A", "SCP2D1","CA9","CCDC80","A NKRD9","FAM209B", "MS4A6E", "C20orf173" "PDCL2", "GPR18", "ASB17", "G2E3","C2orf40", "FAM8A1","CAST", "TEX29", "RNF151","IQGAP2","CLIP4", "CCDC126","RNF141","C1orf1 00","SAXO1", "SUN5","GTSF1L","AKAP3", "OTUB2", "ZNF683","MEX3B", "PPP4R1","TRIM42", "SERP2", "ERICH2","MEX3C", "MAPKAPK2","TEX26", "HEMGN", "TSSK2", "C2orf73", "XYLT2", "AKIRIN1", "DXO","LRRC37A2","MARCH8 ","MKRN2","FBXO39","SPACA4 ","SUN3","NFKBIB","LRRC37A", "TMEM270", "HMGB4", "TMEM191C","TMCO2", "CHD5","DUSP13","CALCOC O2","RFPL3S","C10orf82","SPPL 2C","INPP1", "POLB","CXXC5", "IRGC","SPACA9","C17orf105" "CCDC179", "ZNRF4", "SPACA3","TFAM","TEX37", "SPACA7","ACRV1", "FNDC11","C20orf144"

Elongating spermatid (ES-2) "TRIM42","CCDC179", "HEMGN", "TTLL2", "BAG5","FAM71B","TFAM",

19 "C1orf100","FAM71F1", "TRIM36","EFCAB1","INPP1", "TUBG1", "KIF2B", "C17orf105","SPACA9","HMGB 4","NFKBIB","ACP1","FAM71C", "FAM57A","FBXO39","OTUB2", "COX8C","MARCH8","GOLM1 ", "TNP2","TEX35", "C3orf30", "PRSS58","TEX37", "IQCF2","TSSK1B","UBE2J1","C CDC196","C10orf82","CCSER2 ","TLE4","FAM120B","GLRX2"," BAG1","IQCF1","MAPKAPK2"," SPTY2D1-AS1","LRRD1","TUB A4A","SPATA24", "CA2","HSPA1L", "CDC14A","SPERT", "KNSTRN","DNAJA4","FAM71E 1", "AKAP4", "AKIRIN1", "GSTO2", "TNP1","C2orf88", "FAM81B","RNF151","IRGC","F NDC8","GNG2","CAPZA3","A C010255.3","TEX44","ANKEF1" ,"CEP170","FAM71A","CNN1"," AL672043.1","TSSK2","CKB","H OOK1","GAPDHS","OXCT2"," GTSF1L","CT83","PRM1","RNF1 41","SPATA6","RFPL3S","CXCL1 6", "OAZ3","TSSK6", "TMCO2", "SPATA18", "SH3RF2","CABS1", "AKAP1","LELP1", "TPPP2", "PRM2","GLUL","CRISP2","C20 orf141","ODF1","TMEM31","SA MD4A"

Elongating spermatid (ES-3) "PRM1","LEMD1","TNP1","AC0 10255.3","SPATA19","C9orf24"," IQCF3","TNP2","AL672043.1"," SPEM1","SPATA6","MORN3","T AF10","PRM2","CRISP2","SMCP" ,"TSSK6","SPATA20","ODF1","P CP2","SH3RF2","H1FNT","IQCF

20 1","LELP1","ODF2","PSMF1","FN DC8","SPATA32","PHF7","DYNL L2","ESS2","AKAP1","ARPP19"," TSPAN16","CYLC1","C17orf74" ,"ACSBG2","RNF138","CLMN"," WDR1","FUNDC2","C11orf71", "PAQR7","DCUN1D1","CXCL1 6","TUBA4A","KIF2C","CAPZA 3","TSPAN1", "CA2","C19orf70","SOCS7","N UPR2","IQCF2","TMEM31","OA Z3","TSPAN6","NRDC","GAPD HS","CLPB","TEX44","FSCN3"," SPATA3","DCAF1","CCDC91"," C10orf62","LPIN1","TPPP2","A DIG","GLUL","LINC00854","AC TL7A","C16orf82","AKAP4","UB E2J1","ADRM1","NSUN4","ACA P1","ETNK2","MFAP3L","BAG1", "HOOK1","FAM81B","CABS1"," CEP170","HSPA1L","ACTRT2"," CCSER2","ISG20L2","C12orf54" ,"CCDC54","SPERT","ACE","GP X4","SAMD4A","SPATA18","TE X37","C20orf141","SPTY2D1-A S1","PRH1"

Elongating spermatid (ES-4) "C16orf78", "SPATA3", "GSG1", "PHOSPHO1", "C10orf62", "FSCN3","PRM2", "PROCA1", "CRISP2", "LELP1","MOSPD3", "AC133555.3" "GLUL", "RANGAP1", "DCUN1D1","C16orf82", "MORN3","LPIN1","ACAP1","P AQR7","TCP11", "PCYT2","CLPB", "RNF138", "ACSBG2", "SPATA18","BPIFA3", "FAM46C","GAPDHS","DDX3X ","ZFAND3","SMKR1","TSSK3"," ODF1", "NSUN4", "BOD1L2",

21 "TSSK6","SMCP","MROH7","CA BS1","CXCL16","RND2","DNAJ C4", "AC106782.1" "OAZ3", "C3orf22","MS4A14", "C17orf74", "ODF3L2", "REEP6","NUPR2","ETNK2","C CNY", "TSPAN6", "HIP1", "ABHD1","NDUFA13","CCDC9 1","SPATC1","TPPP2","STPG3"," TSPAN16","FAM71F2","FUNDC 2","ZDHHC19","UBE2N","SPEM 1","RCC1", "PCP2", "RNF44", "MFAP3L","TTC7A","TEX46","P KM","C19orf70", "AZIN2","METAP1", "AKAP1","DNAJB8", "LINC00854","LRRD1","DCAF1 ","AKAP4","CA2", "DGCR6L", "WBP2NL", "ODF2", "SH3RF2", "RAB11FIP4","ACTL7A", "PARD6A","ISG20L2","GPX4", "TPI1", "AL672043.1" "C12orf54", "UBQLNL", "STARD10", "MEX3D","PRM1"

22 Supplementary Table 2

Table 2. Lists of regulon markers from each individual stage during human spermatogenesis.

Stages Marker regulons

Sg-1 "RUNX3","BARHL2","ZNF362","CDX2", "IRX2", "POLR3G","NFATC1","NFIC", "CLOCK","PHF21A","SIX1", "NR2C1","SOX8", "HMGA1","MLXIP", "NR1H2","FOXA1","SMC3", "ESX1", "LHX3", "RFX7", "CTCFL","SOX4", "POU3F1","E2F6", "YY2",,"PAX8", "POLR3A","HMGB1","E2F1", "MAZ",,"IRF3","SMARCC2","ZNF319","FOXK1","JUN",,"TCF12","NR3C1","HSF2 ", "", "MBD1", "ZNF646","FOXP1","GMEB1","ZNF233"

Sg-2 "GLIS3", "POLR3G","NFIC","PHF21A","SIX1","DDIT3", "SOX8","GMEB1", "NR2C1", "HMGA1", "IRX2","SMC3","FOXD2", "ATF6B", "CLOCK", "CTCFL", "ESX1","PAX8","HMGB1", "TCF12", "E2F1","POLR3A","E2F6","SOX4","JUN", "POU3F1","MAZ", "YY2", "SMARCC2" "IRF3", "ZNF319","HSF2","NR3C1", "ZNF646","MYBL1"

Sc-1 "PITX2", "PAX6","TLX2","ATF6B", "ETV6","ZNF579","FOXF2", "CLOCK", "GMEB1", "FOXK1", "POLR3G","RXRB","FOXD2", "HMGA1", "SMC3", "PHF21A","CTCFL","MECOM","ESX1","PAX8","NFATC1","HSF2","IRF3","SMAR CC2" "NR2C1", "E2F1","MAZ", "HMGB1", "ZNF319","POLR3A","YY2", "E2F6","TCF12", "MYBL1", "NR1H2", "JUN", "NR3C1", "ZNF646"

Sc-2 "RXRB","DDIT3", "GMEB1", "POLR3G","FOXD2", "PHF21A","ATF6B", "CLOCK", "SMC3","CTCFL", "PAX8","IRF3","MYBL1", "ZNF319","MAZ", "SMARCC2" "TCF12", "HMGB1", "POLR3A","E2F1","YY2","HSF2"

Sc-3 "LEF1","FOXD2","ZNF546","CLOCK","TCF12","MYBL1","IRF3","MBD1","SMC3", "NR1H2","OVOL1"

Sc-4 "DTL","ZFP64","OVOL1","MBD1","SOX18","MYBL1","ZNF233","ZNF646","KDM4 D","TCF12"

RS-1 "DTL","ZFP64","OVOL1","MBD1","SOX18","MYBL1","ZNF233","ZNF646","KDM4 D","TCF12"

RS-2 "KDM4D","SOX18", "ZNF646", "HSF2", "ZNF233"

RS-3 "HSF2", "KDM4D","BBX","NR3C1","ZNF646"

RS-4 "BBX","GFI1B","NR3C1"

ES-1 "SHOX2","GATA6","BBX","GFI1B","KLF4"

23 ES-2 "GATA6","DUX4","PRKAA1","GFI1B","KLF4"

ES-3 "DUX4","PRKAA1","BCL6","FOXP1"

ES-4 "TAL2","NFE4","FOXB1","PRKAA1","DUX4","ZNF85"

Supplementary Table 3

Table 3. Lists of genes involved in DNA repair pathways consisted of Nuclear excision repair (NER), Base excision repair (BER), Mismatch repair (MMR), Homologous recombination (HR), Non-homologous end joining (NHEJ), and Inter-crosslinking repair (ICL).

Pathway Gene name Reference

Nuclear excision repair "ERCC4","XRCC4","ERCC6", (Boeing et al., 2016; Calmels et (NER) "TCEA1", "ERCC8", "XPC", al., 2016; Cheng et al., 2000; "ERCC1", "POLR2A", "STK19", Friboulet et al., 2013; Gayarre et "RFWD3", "ELOF1", "ERCC2", al., 2016; Joo et al., 2016; Kaina, "UVSSA", "XPA", "GTF2H4", 2020; Kou et al., 2008; Lin et al., "ERCC5", "ERCC3", "POLK", 2018; Lipkowitz and Weissman, "GTF2H1", "GTF2H5", 2011; Lisica et al., 2016; Ma et "RFWD2", "REV3L","MMS19" al., 1994; Manandhar et al., 2015; Nakazawa et al., 2012; Ogi and Lehmann, 2006; Petruseva et al., 2014; Ræder et al., 2018; Rosin et al., 2015; Soltys et al., 2013; Song et al., 2017; Sugitani et al., 2016; Yang et al., 2018)

Base excision repair (BER) "NTHL1", "LIG1", "TDP1", (Limpose et al., 2018; Nazarkina "PARP1", "XRCC1","REV1" et al., 2007; Prasad et al., 2016; Rechkunova et al., 2015; Sukhanova et al., 2010; Sykora et al., 2013)

Mismatch repair (MMR) "MSH2", "MLH1", "MSH6", (Ellison et al., 2004; Kantelinen "PMS2" et al., 2012; Nakagawa et al., 2004)

Homologous recombination "FIGNL1", "RMI1", "BLM", (Amendola et al., 2017; Boudrez

24 (HR) "RMI2", "MCM8", "HROB", et al., 2000; Brenneman et al., "MCM9", "RAD51", "RAD51C", 2002; Brommage et al., 2014; "XRCC3", "BRCA2", "PALB2", Buisson and Masson, 2012; "BRCA1","RAD51B", "NBN", Chon et al., 2009; Couturier et "BARD1", "RAD51D", al., 2016; Domingo-Prim et al., "MRE11A", "XRCC2", "SFR1", 2019; Ertl et al., 2017; Froyen et "EME1", "RAD54L", "AUNIP", al., 2012; Gannavaram et al., "MUS81", "TRAIP", "FEN1", 2014; Gaponova et al., 2017; Gu "SCC1", "DDX11", "RNF8", et al., 2008; Hanada et al., 2006; "XRCC1", "RNASEH2C", Heeke et al., 2018; Hickson and "RNASEH2A", "LMNA", Mankouri, 2011; Hiller et al., "SCAP", "MMGT1", "UFSP2", 2012; Holloman, 2011; Huo et "WDR83", "WDHD1", al., 2020; Hustedt et al., 2019; "ECHS1", "C7orf26","TCEB2", Johnson et al., 1999; Junes-Gill "PPP1R8", "DHX9","SLC25A28", et al., 2014; Kikuchi et al., 2005; "PDS5B", "HUWE1", "MAU2", Konstantinopoulos et al., 2015; "CDK2", "PPP4C", "FOXM1", Lee and Pelletier, 2016; Lou et "CDC25", "ESCO2", "KDM8", al., 2017; Lu et al., 2012; Ma et "STAG1", "JMJD6", "MED12", al., 2017; Matos et al., 2008; "DIS3", "DKC1", "TIPRL", Mondesert et al., 2002; Moon et "DBF4" al., 2012; Nishimura et al., 2012; Pal et al., 2017; Park and Lee, 2020; Redwood et al., 2011; Reh et al., 2017; Singh et al., 2008; Soo Lee et al., 2016; Su et al., 2012; Su et al., 2016; Takata et al., 2000; Tan et al., 2007; van der Lelij et al., 2009; van Schie et al., 2020; Viera et al., 2009; Villoria et al., 2019; Vispé et al., 1998; Walter et al., 1996; Wang and Wang, 2014; Wilson et al., 2012; Wu and Yu, 2012; Wu et al., 2012; Yang et al., 2016; Zha et al., 2009; Zhang, 2013; Zhang et al., 2020; Zhao et al., 2017)

Non-homologous end joining "C7orf49", "ERCC6L2", "POLL", (Chapman et al., 2013; Chifman (NHEJ) "UIMC1", "IREB2", "SHLD2", et al., 2014; Dev et al., 2018; "POLQ","SHLD1", "DCLRE1C", Dianatpour and Ghafouri-Fard, "RIF1" 2017; Felgentreff et al., 2015; Francica et al., 2020; Schimmel

25 et al., 2017; Slavoff et al., 2014; Waters et al., 2014)

Inter-crosslinking repair (ICL) "ESCO1", "FANCD2", "SLX4", (Andreassen and Ren, 2009; "USP1", "DCLRE1A", "FANCG", Deans and West, 2011; Gunn et "C1orf86","C17orf70","FANCM" al., 2016; Huang et al., 2019; , "FANCB", "FANCA", Jiang et al., 2017; Kim et al., "FANCF", "C19orf40", 2012; Leman and Noguchi, "FANCL", "FANCC", "FANCI", 2014; Ling et al., 2007; Liu et al., "TRAIP", "UBE2T","BRIP1" 2010; Murai et al., 2011; Wu et al., 2019; Yamamoto et al., 2011)

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