A transit-amplifying population underpins the efficient regenerative capacity of the testis.
A transit-amplifying population underpins the efficient regenerative capacity of the testis.
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DOI：
10.1084/jem.20161371
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发表时间：
2017-06-05
期刊：
影响因子：
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通讯作者：
O'Carroll D
中科院分区：
文献类型：
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作者：
Carrieri C;Comazzetto S;Grover A;Morgan M;Buness A;Nerlov C;O'Carroll D
Carrieri等人鉴定了一种新的表达Miwi2的未分化精原细胞群体。这个群体在稳态期间表现为过渡放大细胞，但保留兼性干细胞活性，对再生精子发生至关重要。精原干细胞（SSC）在整个成年生活中支持精子发生，位于表达GFRα1的A型未分化精原细胞中。决定致力于生精分化与GFRα1的丧失和Ngn 3（Neurog 3）表达的相互获得相一致。通过分析皮尔纳因子Miwi2（Piwi4），我们鉴定了一种新的Ngn3表达精原细胞群体，这些精原细胞对于损伤后有效的睾丸再生至关重要。Miwi2表达细胞的消耗导致对睾丸稳态的短暂影响，该群体在稳态条件下严格表现为转运扩增细胞。然而，在损伤时，表达Miwi2的细胞对于睾丸的有效再生能力是必不可少的，并且在移植测定中也显示兼性干细胞活性。总之，小鼠睾丸采用了再生策略，通过将过渡扩增群体并入有效的干细胞库来扩大干细胞活性，从而确保快速有效的组织修复。
Carrieri et al. identify a novel population of Miwi2-expressing undifferentiated spermatogonia. This population behave as transit-amplifying cells during homeostasis, but retain facultative stem cell activity and is critical for regenerative spermatogenesis. The spermatogonial stem cell (SSC) that supports spermatogenesis throughout adult life resides within the GFRα1-expressing A type undifferentiated spermatogonia. The decision to commit to spermatogenic differentiation coincides with the loss of GFRα1 and reciprocal gain of Ngn3 (Neurog3) expression. Through the analysis of the piRNA factor Miwi2 (Piwil4), we identify a novel population of Ngn3-expressing spermatogonia that are essential for efficient testicular regeneration after injury. Depletion of Miwi2-expressing cells results in a transient impact on testicular homeostasis, with this population behaving strictly as transit amplifying cells under homeostatic conditions. However, upon injury, Miwi2-expressing cells are essential for the efficient regenerative capacity of the testis, and also display facultative stem activity in transplantation assays. In summary, the mouse testis has adopted a regenerative strategy to expand stem cell activity by incorporating a transit-amplifying population to the effective stem cell pool, thus ensuring rapid and efficient tissue repair.