During human spermatogenesis, germ cells undergo dynamic changes in chromatin organization/re-packaging and in transcriptomes. In order to better understand the underlying mechanism(s), scATAC-Seq of 5376 testicular cells from 3 normal men were performed. Data were analyzed in parallel with the scRNA-Seq data of human testicular cells. In all, 10 germ cell types associated with spermatogenesis and 6 testicular somatic cell types were identified, along with 142 024 peaks located in promoter, genebody and CpG Island. We had examined chromatin accessibility of all chromosomes, with chromosomes 19 and 17 emerged as the leading chromosomes that displayed high chromatin accessibility. In accessible chromatin regions, transcription factor-binding sites were identified and specific motifs with high frequencies at different spermatogenesis stages were detected, including CTCF, BORIS, NFY, DMRT6, EN1, ISL1 and GLI3. Two most remarkable observations were noted. First, TLE3 was specifically expressed in differentiating spermatogonia. Second, PFN4 was found to be involved in actin cytoskeletal organization during meiosis. More important, unique regions upstream of PFN4 and TLE3 were shown to display high accessibility, illustrating their significance in supporting human spermatogenesis.

中文翻译：

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单细胞 ATAC-Seq 揭示了人类精子发生中细胞类型特异性转录调控和独特的染色质可及性

在人类精子发生过程中，生殖细胞在染色质组织/重新包装和转录组中发生动态变化。为了更好地了解潜在机制，对来自 3 名正常男性的 5376 个睾丸细胞进行了 scATAC-Seq。数据与人类睾丸细胞的 scRNA-Seq 数据并行分析。总共鉴定出与精子发生相关的10种生殖细胞类型和6种睾丸体细胞类型，以及位于启动子、基因体和CpG岛的142 024个峰。我们检查了所有染色体的染色质可及性，19 号和 17 号染色体成为显示高染色质可及性的主要染色体。在可接近的染色质区域，鉴定了转录因子结合位点，并检测了在不同精子发生阶段具有高频率的特定基序，包括 CTCF、BORIS、NFY、DMRT6、EN1、ISL1 和 GLI3。注意到两个最显着的观察结果。首先，TLE3 在分化精原细胞中特异性表达。其次，发现 PFN4 在减数分裂过程中参与肌动蛋白细胞骨架组织。更重要的是，PFN4 和 TLE3 上游的独特区域显示出高可达性，说明它们在支持人类精子发生方面的重要性。