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Pluripotency factor NANOG promotes germ cell maintenance in vitro without triggering dedifferentiation of spermatogonial stem cells
Theriogenology ( IF 2.8 ) Pub Date : 2020-05-01 , DOI: 10.1016/j.theriogenology.2020.02.028
Mi Yang , Bingquan Deng , Lei Geng , Lufan Li , Xin Wu

Spermatogonial stem cells (SSCs) are defined as the tissue-specific stem cells in the testes that produce sperm and support life-long spermatogenesis. A culture microenvironment could convert mouse SSCs from unipotent to pluripotent states; however, the underlying mechanism is unclear. NANOG has been considered the decisive transcriptional factor for pluripotency transition of stem cells, but NANOG is not expressed in SSCs. Here, we investigated whether NANOG overexpression could result in SSCs being converted into a pluripotent state. We found that rare NANOG-positive cells could be detected in spermatogonia, pachytene spermatocytes, and even round spermatids in mouse testes, and that the induction of NANOG could promote the proliferation of cultured SSCs in vitro and partially compensate for the role of the growth factor GDNF. In vivo allogeneic transplantation of NANOG-overexpressing germ cells did not yield any teratoma-like tissues, but regenerated normal colonies of spermatogenesis in the testes of recipient mice. Collectively, our data showed that overexpression of the pluripotency factor NANOG along did not dedifferentiate testis germline stem cells into a pluripotent state, suggesting that other genetic or epigenetic factors are involved in SSC reprogramming.

中文翻译:

多能性因子 NANOG 在体外促进生殖细胞维持而不触发精原干细胞的去分化

精原干细胞 (SSC) 被定义为睾丸中产生精子并支持终生精子发生的组织特异性干细胞。培养微环境可以将小鼠 SSC 从单能状态转变为多能状态;然而,潜在的机制尚不清楚。NANOG 被认为是干细胞多能性转变的决定性转录因子,但 NANOG 在 SSC 中不表达。在这里,我们调查了 NANOG 过表达是否会导致 SSC 转化为多能状态。我们发现在小鼠睾丸的精原细胞、粗线期精母细胞甚至圆形精细胞中都可以检测到罕见的NANOG阳性细胞,并且NANOG的诱导可以促进体外培养的SSCs的增殖并部分补偿生长因子的作用GDNF。NANOG 过表达生殖细胞的体内同种异体移植没有产生任何畸胎瘤样组织,但在受体小鼠的睾丸中再生了正常的精子发生集落。总的来说,我们的数据表明,多能性因子 NANOG 的过度表达不会使睾丸生殖系干细胞去分化为多能状态,这表明其他遗传或表观遗传因素参与了 SSC 重编程。
更新日期:2020-05-01
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