TAF4b is required for mouse spermatogonial stem cell development.

TAF4b is required for mouse spermatogonial stem cell development.
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DOI:
10.1002/stem.1914
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发表时间:
2015-04
期刊:
影响因子:
5.2
通讯作者:
Freiman, Richard N.
Freiman, Richard N.
中科院分区:
医学2区
文献类型:
--
作者:
Lovasco, Lindsay A.;Gustafson, Eric A.;Seymour, Kimberly A.;de Rooij, Dirk G.;Freiman, Richard N.

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哺乳动物的长期精子发生需要精原干细胞(SSCs)的适当发育,在成年过程中,SSCs用生殖细胞前体细胞补充睾丸。TAF4b是一般转录因子复合体TFIID的性腺富集组分,是维持小鼠精子发生所必需的。对TAF4b缺陷的成人宿主睾丸的成功生殖细胞移植试验表明,TAF4b在SSC的建立和/或维持中发挥着重要的生殖细胞自主功能。为了阐明TAF4b的SSC功能,我们在TAF4b缺陷的小鼠睾丸中研究了原始生殖细胞池和几轮生精分化。在这里,我们展示了胚胎晚期性细胞池的显着减少,以及出生后不久这个池的缺陷扩张。与年龄匹配的对照组相比,生殖细胞前体细胞的减少导致减数分裂启动的发育延迟。GfRα1+精原细胞在野生型睾丸中以单个和成对的形式存在,而缺乏TAF4b的精原细胞显示GfRα1+细胞的长链和聚集链的比例增加。在缺乏TAF4b的情况下,成人睾丸中的生精小管要么完全缺乏生殖细胞,要么被发现缺失几代生精祖细胞。综上所述,这些数据表明,TAF4b缺陷的生精前体细胞表现出以自我更新为代价的分化趋势,在SSC发育的关键窗口未能建立SSCs更新池。
Long-term mammalian spermatogenesis requires proper development of spermatogonial stem cells (SSCs) that replenish the testis with germ cell progenitors during adult life. TAF4b is a gonadal-enriched component of the general transcription factor complex, TFIID, which is required for the maintenance of spermatogenesis in the mouse. Successful germ cell transplantation assays into adult TAF4b-deficient host testes suggested that TAF4b performs an essential germ cell autonomous function in SSC establishment and/or maintenance. To elucidate the SSC function of TAF4b, we characterized the initial gonocyte pool and rounds of spermatogenic differentiation in the context of the Taf4b-deficient mouse testis. Here we demonstrate a significant reduction in the late embryonic gonocyte pool and a deficient expansion of this pool soon after birth. Resulting from this reduction of germ cell progenitors is a developmental delay in meiosis initiation, as compared to age-matched controls. While GFRα1+ spermatogonia are appropriately present as Asingle and Apaired in wild type testes, TAF4b-deficient testes display an increased proportion of long and clustered chains of GFRα1+ cells. In the absence of TAF4b, seminiferous tubules in the adult testis either lack germ cells altogether or are found to have missing generations of spermatogenic progenitor cells. Together these data indicate that TAF4b-deficient spermatogenic progenitor cells display a tendency for differentiation at the expense of self-renewal and a renewing pool of SSCs fail to establish during the critical window of SSC development.
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