Identification of dynamic undifferentiated cell states within the male germline.
Identification of dynamic undifferentiated cell states within the male germline.
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DOI：
10.1038/s41467-018-04827-z
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发表时间：
2018-07-19
影响因子：
16.6
通讯作者：
Hobbs RM
中科院分区：
文献类型：
--
作者：
La HM;Mäkelä JA;Chan AL;Rossello FJ;Nefzger CM;Legrand JMD;De Seram M;Polo JM;Hobbs RM
干细胞在组织维持中的作用受到重视，并且经常提出干细胞自我更新和分化的分层模型。雄性生殖系中的干细胞活性仅限于未分化的 A 型精原细胞 (Aundiff)；然而，这一群体中只有一小部分在未受干扰的睾丸中充当干细胞，并且 Aundiff 等级制度仍然存在争议。通过新开发的复合报告小鼠，我们定义了自我更新和分化引发的成年 Aundiff 部分的分子特征，并通过单细胞分析剖析了 Aundiff 异质性。我们在自我更新的 Aundiff 部分中发现了一个未被重视的群体，其标志是胚胎模式基因和同源域转录因子 PDX1 的表达。重要的是，我们发现 PDX1 标记了一个具有成熟、稳态睾丸特有的强大干细胞能力的群体，并在移植和培养时表现出 PDX1+ 和 PDX1− Aundiff 状态之间的动态相互转换。我们得出结论，Aundiff 存在于一系列具有不同功能的动态细胞状态中，并提供证据表明这些状态的稳定性是由生态位衍生的线索决定的。持续的精子发生取决于未分化精原细胞群中包含的干细胞活性。在这里，作者在成人睾丸中发现了一个新的未分化精原细胞群，它们表达转录因子 PDX1 并具有干细胞能力。
The role of stem cells in tissue maintenance is appreciated and hierarchical models of stem cell self-renewal and differentiation often proposed. Stem cell activity in the male germline is restricted to undifferentiated A-type spermatogonia (Aundiff); however, only a fraction of this population act as stem cells in undisturbed testis and Aundiff hierarchy remains contentious. Through newly developed compound reporter mice, here we define molecular signatures of self-renewing and differentiation-primed adult Aundiff fractions and dissect Aundiff heterogeneity by single-cell analysis. We uncover an unappreciated population within the self-renewing Aundiff fraction marked by expression of embryonic patterning genes and homeodomain transcription factor PDX1. Importantly, we find that PDX1 marks a population with potent stem cell capacity unique to mature, homeostatic testis and demonstrate dynamic interconversion between PDX1+ and PDX1− Aundiff states upon transplant and culture. We conclude that Aundiff exist in a series of dynamic cell states with distinct function and provide evidence that stability of such states is dictated by niche-derived cues. Sustained spermatogenesis depends on stem cell activity which is contained within a population of undifferentiated spermatogonia. Here, the authors identify a new population of undifferentiated spermatogonia in adult testis that expresses the transcription factor PDX1 and has stem cell capacity.
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影响因子：
5.9
作者：
Chan AL;La HM;Legrand JMD;Mäkelä JA;Eichenlaub M;De Seram M;Ramialison M;Hobbs RM
通讯作者：
Hobbs RM
影响因子：
64.5
作者：
Hobbs RM;Seandel M;Falciatori I;Rafii S;Pandolfi PP
通讯作者：
Pandolfi PP
影响因子：
5.2
作者：
Hasegawa, Kazuteru;Namekawa, Satoshi H.;Saga, Yumiko
通讯作者：
Saga, Yumiko
影响因子：
23.9
作者：
Hara, Kenshiro;Nakagawa, Toshinori;Enomoto, Hideki;Suzuki, Mikiko;Yamamoto, Masayuki;Simons, Benjamin D.;Yoshida, Shosei
通讯作者：
Yoshida, Shosei
小鼠睾丸中ID4+种系干细胞群的功能和分子特征。
影响因子：
10.5
作者：
Chan F;Oatley MJ;Kaucher AV;Yang QE;Bieberich CJ;Shashikant CS;Oatley JM
通讯作者：
Oatley JM