PAX7 expression defines germline stem cells in the adult testis
PAX7 expression defines germline stem cells in the adult testis
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DOI：
10.1172/jci75943
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发表时间：
2014-09-01
影响因子：
15.9
通讯作者：
Castrillon, Diego H.
中科院分区：
文献类型：
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作者：
Aloisio, Gina M.;Nakada, Yuji;Castrillon, Diego H.
精子发生是一个复杂的、多步骤的过程，它维持了男性的生育能力，并由罕见的生殖系干细胞维持。生精进程始于精原细胞，其种群表达不同的标记。由于缺乏可靠和特异性的标记物，未受干扰的睾丸中的精原干细胞群的身份是有争议的。在这里，我们发现转录因子PAX7（+）是小鼠a（单）精原细胞罕见亚群的特异性标记。出生时睾丸中存在PAX7（+）细胞。与成年睾丸相比，PAX7（+）细胞在新生生殖细胞中所占的比例要高得多。对健康成年小鼠的谱系追踪显示，PAX7（+）精原细胞自我维持并产生扩增克隆，产生成熟精子。有趣的是，在接受化疗和放疗的小鼠中，PAX7（+）精原细胞选择性存活，并且它们随后的扩张有助于精子发生的恢复。化疗和放疗都会损伤绝大多数生殖细胞并导致不育。最后，PAX7（+）精原细胞存在于多种哺乳动物的睾丸中。我们的数据表明，A（单一）精原细胞的PAX7（+）亚群作为健壮的睾丸干细胞，在健康小鼠的正常精子发生中维持生育能力，并在严重的种系损伤（如癌症治疗后发生的损伤）后介导恢复。
Spermatogenesis is a complex, multistep process that maintains male fertility and is sustained by rare germline stem cells. Spermatogenic progression begins with spermatogonia, populations of which express distinct markers. The identity of the spermatogonial stem cell population in the undisturbed testis is controversial due to a lack of reliable and specific markers. Here we identified the transcription factor PAX7(+) as a specific marker of a rare subpopulation of A(single) spermatogonia in mice. PAX7(+) cells were present in the testis at birth. Compared with the adult testis, PAX7(+) cells constituted a much higher percentage of neonatal germ cells. Lineage tracing in healthy adult mice revealed that PAX7(+) spermatogonia self-maintained and produced expanding clones that gave rise to mature spermatozoa. Interestingly, in mice subjected to chemotherapy and radiotherapy, both of which damage the vast majority of germ cells and can result in sterility, PAX7(+) spermatogonia selectively survived, and their subsequent expansion contributed to the recovery of spermatogenesis. Finally, PAX7(+) spermatogonia were present in the testes of a diverse set of mammals. Our data indicate that the PAX7(+) subset of A(single) spermatogonia functions as robust testis stem cells that maintain fertility in normal spermatogenesis in healthy mice and mediate recovery after severe germline injury, such as occurs after cancer therapy.