南方医科大学赵小阳、高帅和常港研究组合作探明，人类精子发生的单细胞多组学测序揭示了与雄性减数分裂重组相关的DNA去甲基化事件。这一研究成果于2023年9月18日发表在国际顶尖学术期刊《自然—细胞生物学》上。

通过使用改进的单细胞染色质整体基因组尺度景观测序方法同时研究染色质可及性、DNA甲基组和转录组景观，他们发现人类精子发生过程中的转录变化与染色质可及性变化相关。特别是，他们确定了一组具有潜在功能的转录因子和顺式元件。在人类精子发生过程中，发现了与雄性减数分裂重组有关的DNA去甲基化过程，该过程在人类和小鼠之间具有保守性。在某些非阻塞性无精子症患者的瘦素精细胞中可检测到异常的DNA高甲基化。

在功能上，DNA去甲基化的干预影响了雄性减数分裂重组和生育。他们的工作在单细胞分辨率下提供了人类精子发生的多组学景观，并提供了DNA去甲基化和男性减数分裂重组之间关系的见解。

据了解，人类精子发生是一个高度有序的过程;然而，DNA甲基化和染色质可及性在这一过程中的作用在很大程度上仍然未知。

附：英文原文

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

Author: Huang, Yaping, Li, Lin, An, Geng, Yang, Xinyan, Cui, Manman, Song, Xiuling, Lin, Jing, Zhang, Xiaoling, Yao, Zhaokai, Wan, Cong, Zhou, Cai, Zhao, Jiexiang, Song, Ke, Ren, Shaofang, Xia, Xinyu, Fu, Xin, Lan, Yu, Hu, Xuesong, Wang, Wen, Wang, Mei, Zheng, Yi, Miao, Kai, Bai, Xiaochun, Hutchins, Andrew P., Chang, Gang, Gao, Shuai, Zhao, Xiao-Yang

Issue&Volume: 2023-09-18

Abstract: 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.

DOI: 10.1038/s41556-023-01232-7

Source: https://www.nature.com/articles/s41556-023-01232-7