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人类、猕猴和小鼠睾丸的单细胞 RNA 测序揭示了哺乳动物精子发生的保守和分化特征。

Single-Cell RNA Sequencing of Human, Macaque, and Mouse Testes Uncovers Conserved and Divergent Features of Mammalian Spermatogenesis.

机构信息

Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.

Department of Obstetrics, Gynecology, and Reproductive Sciences, Integrative Systems Biology Graduate Program, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

出版信息

Dev Cell. 2020 Aug 24;54(4):529-547.e12. doi: 10.1016/j.devcel.2020.05.010. Epub 2020 Jun 5.

Abstract

Spermatogenesis is a highly regulated process that produces sperm to transmit genetic information to the next generation. Although extensively studied in mice, our current understanding of primate spermatogenesis is limited to populations defined by state-specific markers from rodent data. As between-species differences have been reported in the duration and differentiation hierarchy of this process, it remains unclear how molecular markers and cell states are conserved or have diverged from mice to man. To address this challenge, we employ single-cell RNA sequencing to identify transcriptional signatures of major germ and somatic cell types of the testes in human, macaque, and mice. This approach reveals similarities and differences in expression throughout spermatogenesis, including the stem/progenitor pool of spermatogonia, markers of differentiation, potential regulators of meiosis, RNA turnover during spermatid differentiation, and germ cell-soma communication. These datasets provide a rich foundation for future targeted mechanistic studies of primate germ cell development and in vitro gametogenesis.

摘要

精子发生是一个高度调控的过程,产生精子将遗传信息传递给下一代。尽管在小鼠中进行了广泛研究,但我们目前对灵长类动物精子发生的理解仅限于基于啮齿动物数据的特定状态标记定义的群体。由于在这个过程的持续时间和分化层次上存在种间差异,因此仍不清楚分子标记和细胞状态在从老鼠到人类的过程中是如何保守或分化的。为了解决这一挑战,我们采用单细胞 RNA 测序来鉴定人类、猕猴和小鼠睾丸中主要生殖和体细胞类型的转录特征。这种方法揭示了精子发生过程中表达的相似性和差异,包括精原干细胞/祖细胞池、分化标志物、减数分裂潜在调节剂、精子细胞分化过程中的 RNA 周转以及生殖细胞-体细胞通讯。这些数据集为未来针对灵长类动物生殖细胞发育和体外配子发生的机制研究提供了丰富的基础。

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