PTEN signaling is required for the maintenance of spermatogonial stem cells in mouse, by regulating the expressions of PLZF and UTF1.

PTEN signaling is required for the maintenance of spermatogonial stem cells in mouse, by regulating the expressions of PLZF and UTF1.
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DOI:
10.1186/s13578-015-0034-x
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发表时间:
2015
期刊:
影响因子:
7.5
通讯作者:
Yu Z
Yu Z
中科院分区:
生物学2区
文献类型:
--
作者:
Zhou W;Shao H;Zhang D;Dong J;Cheng W;Wang L;Teng Y;Yu Z

文献摘要

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Pten 在一些器官的干细胞维持中起着至关重要的作用。 Pten缺陷还会导致卵母细胞过早和卵巢老化。我们和其他团队发现磷脂酰肌醇-3-OH 激酶 (PI3K)-Akt 信号传导可调节精原干细胞 (SSC) 的增殖和分化。 PTEN 充当 PI3K 通路的负调节因子。因此,我们认为SSC的命运可能由Pten控制。我们报道早幼粒细胞白血病锌指 (PLZF) 和未分化胚胎细胞转录因子 1 (UTF1) 都是生殖细胞特异性转录因子,均受 Pten 调节。 Pten 的条件性缺失会导致 PLZF 表达减少,但会诱导 UTF1,这与男性随年龄增长的 SSC 耗竭和不育有关。我们的数据表明,Pten 是小鼠 SSC 的长期维持和精子发生的精确调节所必需的。 Pten 调节的 GFRα1+/PLZF−/UTF1+ 祖细胞群的发现为控制 SSC 命运的精确机制提供了新的见解。本文的在线版本 (doi:10.1186/s13578-015-0034-x) 包含补充材料,可供授权用户使用。
Pten plays a crucial role in the stem cell maintenance in a few organs. Pten defect also causes the premature oocytes and ovary aging. We and other groups have found that the phosphatidylinositol-3-OH kinase (PI3K)-Akt signaling regulates the proliferation and differentiation of spermatogonial stem cells (SSCs). PTEN functions as a negative regulator of the PI3K pathway. Thus, we thought that the fate of SSCs might be controlled by Pten. We report that promyelocytic leukaemia zinc finger (PLZF) and undifferentiated embryonic cell transcription factor 1 (UTF1), both of which are germ cell-specific transcriptional factors, are regulated by Pten. Conditional deletion of Pten leads to reduction in PLZF expression but induction of UTF1, which is associated with SSCs depletion and infertility in males with age. Our data demonstrate that Pten is required for the long-term maintenance of SSCs and precise regulation of spermatogenesis in mouse. The finding of a Pten-regulated GFRα1+/PLZF−/UTF1+ progenitor population provides a new insight into the precise mechanisms controlling SSC fate. The online version of this article (doi:10.1186/s13578-015-0034-x) contains supplementary material, which is available to authorized users.