The Dynamic Transcriptional Cell Atlas of Testis Development during Human Puberty

The Dynamic Transcriptional Cell Atlas of Testis Development during Human Puberty
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DOI:
10.1016/j.stem.2019.12.005
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发表时间:
2020-02-06
期刊:
影响因子:
23.9
通讯作者:
Cairns, Bradley R.
Cairns, Bradley R.
中科院分区:
医学1区
文献类型:
--
作者:
Guo, Jingtao;Nie, Xichen;Cairns, Bradley R.

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人类睾丸在青春期经历了巨大的发育和结构变化,包括体细胞龛细胞的增殖和成熟,以及精子发生的开始。为了表征这个未充分研究的过程,我们分析了来自四个青春期男孩的近似10,000个睾丸细胞的单细胞转录组,并将其与婴儿和成人的睾丸细胞进行了比较。在青春期,未分化的精原细胞在配子发生开始之前依次扩增和分化。值得注意的是,我们确定了一个共同的青春期前的Leydig和肌样细胞的祖细胞,并描绘候选因素控制青春期分化。此外,青春期前的支持细胞表现出两种不同的转录状态,不同的代谢谱之前收敛到一个替代的单一成熟人口在青春期。通过对睾酮抑制的transfemale睾丸的单细胞分析,进一步强调了睾酮在支持细胞成熟、抗菌肽分泌和精原细胞分化中的作用。总之,我们的人类睾丸发育的转录图谱提供了多种见解的发展变化和伴随男性青春期的关键因素。
The human testis undergoes dramatic developmental and structural changes during puberty, including proliferation and maturation of somatic niche cells, and the onset of spermatogenesis. To characterize this understudied process, we profiled and analyzed single-cell transcriptomes of similar to 10,000 testicular cells from four boys spanning puberty and compared them to those of infants and adults. During puberty, undifferentiated spermatogonia sequentially expand and differentiate prior to the initiation of gametogenesis. Notably, we identify a common pre-pubertal progenitor for Leydig and myoid cells and delineate candidate factors controlling pubertal differentiation. Furthermore, pre-pubertal Sertoli cells exhibit two distinct transcriptional states differing in metabolic profiles before converging to an alternative single mature population during puberty. Roles for testosterone in Sertoli cell maturation, antimicrobial peptide secretion, and spermatogonial differentiation are further highlighted through single-cell analysis of testosterone-suppressed transfemale testes. Taken together, our transcriptional atlas of the developing human testis provides multiple insights into developmental changes and key factors accompanying male puberty.