Single-cell multi-omics sequencing of human spermatogenesis reveals a DNA demethylation event associated with male meiotic recombination

Huang, Yaping1; Li, Lin2; An, Geng3; Yang, Xinyan1; Cui, Manman1; Song, Xiuling1; Lin, Jing1; Zhang, Xiaoling1; Yao, Zhaokai1; Wan, Cong1; Zhou, Cai1; Zhao, Jiexiang1; Song, Ke1; Ren, Shaofang1; Xia, Xinyu1; Fu, Xin3; Lan, Yu3; Hu, Xuesong1; Wang, Wen1; Wang, Mei1; Zheng, Yi1; Miao, Kai4; Bai, Xiaochun1; Hutchins, Andrew P.5; Chang, Gang6; Gao, Shuai7; Zhao, Xiao-Yang1,8,9,10,11

2023-09-01

10.1038/s41556-023-01232-7

NATURE CELL BIOLOGY   Impact Factor & Quartile

1465-7392

1476-4679

["Human spermatogenesis is a highly ordered process; however, the roles of DNA methylation and chromatin accessibility in this process remain largely unknown. Here by simultaneously investigating the chromatin accessibility, DNA methylome and transcriptome landscapes using the modified single-cell chromatin overall omic-scale landscape sequencing approach, we revealed that the transcriptional changes throughout human spermatogenesis were correlated with chromatin accessibility changes. In particular, we identified a set of transcription factors and cis elements with potential functions. A round of DNA demethylation was uncovered upon meiosis initiation in human spermatogenesis, which was associated with male meiotic recombination and conserved between human and mouse. Aberrant DNA hypermethylation could be detected in leptotene spermatocytes of certain nonobstructive azoospermia patients. Functionally, the intervention of DNA demethylation affected male meiotic recombination and fertility. Our work provides multi-omics landscapes of human spermatogenesis at single-cell resolution and offers insights into the association between DNA demethylation and male meiotic recombination.","Huang, Li, An, Yang, Cui et al. perform a single-cell multi-omics analysis of human spermatogenesis and identify a DNA demethylation event upon meiosis initiation, which is associated with meiotic recombination."]

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Shanghai Institute of Biochemistry and Cell Biology["2022YFA0806303","2022YFC2702603","2021YFA1102700","2020YFA0113300","2019YFA0801802","2019YFE0109500"] ; National Key Ramp;amp;D Programme of China["U22A20278","82071711","31970814","31970787","32170869","32070833","82101745","32170866"] ; National Natural Science Foundation of China[2022B1515020110] ; Natural Science Funds for Distinguished Young Scholar of Guangdong Province[JCYJ20210324120212033] ; Natural Science Foundation of Shenzhen[2020B1111100011]

Cell Biology

Cell Biology

WOS:001069358300001

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MOLECULAR BIOLOGY & GENETICS

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1.Southern Med Univ, Sch Basic Med Sci, Dept Dev Biol, State Key Lab Organ Failure Res, Guangzhou, Peoples R China
2.Southern Med Univ, Sch Basic Med Sci, Dept Pathophysiol, Guangdong Prov Key Lab Proteom, Guangzhou, Peoples R China
3.Guangzhou Med Univ, Affiliated Hosp 3, Dept Reprod Med Ctr, Guangzhou, Peoples R China
4.Univ Macau, Fac Hlth Sci, Ctr Precis Med Res & Training, Taipa, Macau, Peoples R China
5.Southern Univ Sci & Technol, Sch Life Sci, Dept Syst Biol, Shenzhen, Peoples R China
6.Shenzhen Univ, Sch Med, Dept Biochem & Mol Biol, Shenzhen, Peoples R China
7.China Agr Univ, Coll Anim Sci & Technol, Natl Engn Lab Anim Breeding, State Key Lab Anim Biotech Breeding,Key Lab Anim G, Beijing, Peoples R China
8.Southern Med Univ, Guangdong Key Lab Construction & Detect Tissue Eng, Guangzhou, Peoples R China
9.Minist Educ, Key Lab Mental Hlth, Guangzhou, Peoples R China
10.Southern Med Univ, Zhujiang Hosp, Dept Gynecol, Guangzhou, Peoples R China
11.Natl Clin Res Ctr Kidney Dis, Guangzhou, Peoples R China

Huang, Yaping,Li, Lin,An, Geng,et al. Single-cell multi-omics sequencing of human spermatogenesis reveals a DNA demethylation event associated with male meiotic recombination[J]. NATURE CELL BIOLOGY,2023.

Huang, Yaping.,Li, Lin.,An, Geng.,Yang, Xinyan.,Cui, Manman.,...&Zhao, Xiao-Yang.(2023).Single-cell multi-omics sequencing of human spermatogenesis reveals a DNA demethylation event associated with male meiotic recombination.NATURE CELL BIOLOGY.

Huang, Yaping,et al."Single-cell multi-omics sequencing of human spermatogenesis reveals a DNA demethylation event associated with male meiotic recombination".NATURE CELL BIOLOGY (2023).