KDM1A/LSD1 regulates the differentiation and maintenance of spermatogonia in mice.

KDM1A/LSD1 regulates the differentiation and maintenance of spermatogonia in mice.
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DOI:
10.1371/journal.pone.0177473
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发表时间:
2017
期刊:
影响因子:
3.7
通讯作者:
Katz DJ
Katz DJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Myrick DA;Christopher MA;Scott AM;Simon AK;Donlin-Asp PG;Kelly WG;Katz DJ

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精子发生的适当调节对于确保精子的持续产生和生育力至关重要。在这里,我们研究了H3 K4 me 2去甲基化酶KDM 1A/LSD 1在发育和成年小鼠精子发生过程中的功能。出生前睾丸中Kdm 1a的条件性缺失导致3周龄前精原细胞和生殖细胞损失减少。这些结果表明,KDM 1A是所需的精原细胞分化,以及生殖细胞的存活,在发育中的睾丸。此外,在成年睾丸中可诱导的Kdm 1a缺失导致减数分裂精母细胞的异常积累,以及细胞凋亡和进行性生殖细胞损失。这些结果表明,KDM 1A也需要在成人精子发生。此外,在没有KDM 1A的情况下,干细胞因子OCT 4异位维持在分化的生殖细胞中。这种对KDM 1A的需求与在其他干细胞群体中观察到的相似,表明了共同的功能。综上所述,我们认为KDM 1A是小鼠精子发生和生殖细胞维持的关键调节因子。
The proper regulation of spermatogenesis is crucial to ensure the continued production of sperm and fertility. Here, we investigated the function of the H3K4me2 demethylase KDM1A/LSD1 during spermatogenesis in developing and adult mice. Conditional deletion of Kdm1a in the testis just prior to birth leads to fewer spermatogonia and germ cell loss before 3 weeks of age. These results demonstrate that KDM1A is required for spermatogonial differentiation, as well as germ cell survival, in the developing testis. In addition, inducible deletion of Kdm1a in the adult testis results in the abnormal accumulation of meiotic spermatocytes, as well as apoptosis and progressive germ cell loss. These results demonstrate that KDM1A is also required during adult spermatogenesis. Furthermore, without KDM1A, the stem cell factor OCT4 is ectopically maintained in differentiating germ cells. This requirement for KDM1A is similar to what has been observed in other stem cell populations, suggesting a common function. Taken together, we propose that KDM1A is a key regulator of spermatogenesis and germ cell maintenance in the mouse.
DOI: 10.1186/1756-8935-5-18
发表时间: 2012-11-21
影响因子: 3.9
作者:
Brown JP;Bullwinkel J;Baron-Lühr B;Billur M;Schneider P;Winking H;Singh PB
通讯作者: Singh PB