Single-Cell RNA Sequencing Analysis Reveals Sequential Cell Fate Transition during Human Spermatogenesis
Single-Cell RNA Sequencing Analysis Reveals Sequential Cell Fate Transition during Human Spermatogenesis
复制标题
单细胞 RNA 测序分析揭示人类精子发生过程中细胞命运的顺序转变
DOI：
10.1016/j.stem.2018.08.007
复制
发表时间：
2018-10-04
期刊：
影响因子：
23.9
通讯作者：
Qiao, Jie
中科院分区：
文献类型：
--
作者：
Wang, Mei;Liu, Xixi;Qiao, Jie
精子发生产生成熟的雄性配子，对遗传信息在代之间的正确传递至关重要。然而，人类精子发生的发育景观仍然未知。在这里，我们对来自正常精子发生供者的2,854个睾丸细胞和来自非阻塞性无精子症（NOA）供者的174个睾丸细胞进行了单细胞RNA测序（scRNA-seq）分析。建立了3种精原细胞亚型、7种精母细胞亚型和4种精母细胞亚型依次发育的分级模型。进一步分析发现了人类生殖细胞的几个阶段特异性标记基因，如HMGA1、PIWIL4、TEX29、SCML1和CCDC112。此外，通过scRNA-seq分析，我们在一名NOA患者的睾丸体细胞中发现了基因表达模式的改变，为进一步诊断男性不育铺平了道路。我们的工作允许重建人类精子发生过程中固有的序列细胞命运转变的转录程序，并对破译男性相关生殖疾病具有启示意义。
Spermatogenesis generates mature male gametes and is critical for the proper transmission of genetic information between generations. However, the developmental landscapes of human spermatogenesis remain unknown. Here, we performed single-cell RNA sequencing (scRNA-seq) analysis for 2,854 testicular cells from donors with normal spermatogenesis and 174 testicular cells from one nonobstructive azoospermia (NOA) donor. A hierarchical model was established, which was characterized by the sequential and stepwise development of three spermatogonia subtypes, seven spermatocyte subtypes, and four spermatid subtypes. Further analysis identified several stage-specific marker genes of human germ cells, such as HMGA1, PIWIL4, TEX29, SCML1, and CCDC112. Moreover, we identified altered gene expression patterns in the testicular somatic cells of one NOA patient via scRNA-seq analysis, paving the way for further diagnosis of male infertility. Our work allows for the reconstruction of transcriptional programs inherent to sequential cell fate transition during human spermatogenesis and has implications for deciphering male-related reproductive disorders.