Meiosis is a highly complex process significantly influenced by transcriptional regulation. However, studies on the mechanisms that govern transcriptomic changes during meiosis, especially in prophase I, are limited. Here, we performed single-cell ATAC-seq of human testis tissues and observed reprogramming during the transition from zygotene to pachytene spermatocytes. This event, conserved in mice, involved the deactivation of genes associated with meiosis after reprogramming and the activation of those related to spermatogenesis before their functional onset. Furthermore, we identified 282 transcriptional regulators (TRs) that underwent activation or deactivation subsequent to this process. Evidence suggested that physical contact signals from Sertoli cells may regulate these TRs in spermatocytes, while secreted ENHO signals may alter metabolic patterns in these cells. Our results further indicated that defective transcriptional reprogramming may be associated with non-obstructive azoospermia (NOA). This study revealed the importance of both physical contact and secreted signals between Sertoli cells and germ cells in meiotic progression.
减数分裂是一个复杂且精细的生物学过程，其中转录调节扮演着至关重要的角色。我们通过对健康男性睾丸组织进行单细胞ATACseq，发现在减数分裂的前期，具体为偶线期向粗线期过渡的过程中，精母细胞发生了一次转录重编程过程。这一过程在小鼠中也存在，与减数分裂相关的基因在重编程后停止活动，而与精子形成相关的基因则开始被激活。进一步，我们确定了282个在这一重编程过程中被激活或抑制的转录调控因子，并且我们发现从支持细胞发出的物理接触信号可能会调控精母细胞中这些因子的表达。另外，我们也发现分泌型信号分子ENHO在调整精母细胞的代谢模式中可能具有显著作用。最后，通过非梗阻无精子症（NOA）病人睾丸组织单细胞测序数据，我们发现在NOA病人的粗线期精母细胞中存在转录重编程序的缺陷。总之，我们发现了生精细胞减数分裂过程中保守且重要的转录重编程过程，并强调了支持细胞与生殖细胞之间的物理和分泌信号交流对于减数分裂进程的重要性。.
Keywords: Cell-cell communication; Meiosis; Single-cell ATAC-seq; Single-cell RNA-seq; Spermatogenesis; Transcriptional reprogramming.