Single-cell multi-omics sequencing of human spermatogenesis reveals a DNA demethylation event associated with male meiotic recombination
Single-cell multi-omics sequencing of human spermatogenesis reveals a DNA demethylation event associated with male meiotic recombination
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DOI：
10.1038/s41556-023-01232-7
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发表时间：
2023-09
影响因子：
21.3
通讯作者：
Yaping Huang;Lin Li;Geng An;Xinyan Yang;Manman Cui;Xiuling Song;Jing Lin;Xiaoling Zhang
中科院分区：
文献类型：
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作者：
Yaping Huang;Lin Li;Geng An;Xinyan Yang;Manman Cui;Xiuling Song;Jing Lin;Xiaoling Zhang
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。在这里，通过同时调查染色质可及性，DNA甲基化组和转录组景观使用修改的单细胞染色质整体组规模景观测序方法，我们发现，转录变化在整个人类精子发生与染色质可及性的变化。特别是，我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，减数分裂起始时存在一轮DNA去甲基化过程，这一过程与雄性减数分裂重组有关，并且在人类和小鼠之间是保守的。在某些非梗阻性无精子症患者的细线期精母细胞中可以检测到异常的DNA超甲基化。在功能上，DNA去甲基化的干预影响雄性减数分裂重组和生育力。我们的工作提供了单细胞分辨率的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的关联的见解。
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 andciselements 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.