Pluripotency of a single spermatogonial stem cell in mice
Pluripotency of a single spermatogonial stem cell in mice
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DOI：
10.1095/biolreprod.107.066068
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发表时间：
2008-04-01
影响因子：
3.6
通讯作者：
Shinohara, Takashi
中科院分区：
文献类型：
--
作者：
Kanatsu-Shinohara, Mito;Lee, Jiyoung;Shinohara, Takashi
尽管最近在出生后的睾丸中发现了多能干细胞，但对其发育潜力的分析导致了相互矛盾的说法，即精原干细胞是多能的，或者在转化为多能干细胞后失去了生精能力。为了研究这个问题，我们分析了在转基因实验中出现的单个精原干细胞的发育命运。将新霉素抗性基因导入生殖系干细胞后，我们获得了一株类似胚胎干细胞的多能生殖系干细胞。Southern杂交分析表明，种系和多能种系克隆具有相同的转基因整合模式，表明它们具有相同的来源。然而，这两个品系具有不同的DNA甲基化模式。多能生殖系干细胞在胚泡注射后形成嵌合体，但在生殖细胞移植后不产生精子，而生殖系干细胞只能产生精子，不能分化为体细胞。有趣的是，生殖系干细胞表达了几种转录因子(Pou5f1、Sox2、Myc和KIf4)，这是将成纤维细胞重新编程为多能状态所需的，这表明它们具有潜在的多能性。因此，我们的研究提供了证据表明，单个精原干细胞可以获得多潜能，但转化为多能细胞类型伴随着生精潜力的丧失。
Although pluripotent stem cells were recently discovered in postnatal testis, attempts to analyze their developmental potential have led to conflicting claims that spermatogonial stem cells are pluripotent or that they lose spermatogenic potential after conversion into pluripotent stem cells. TO 11 examine this issue, we analyzed the developmental fate of a single spermatogonial stem cell that appeared during transfection experiments. After transfection of a neomycin-resistance gene into germline stem cells, we obtained an embryonic stem-like, multipotent germline stem cell line. Southern blot analysis revealed that the germline stem and multipotent germline stem clones have the same transgene integration pattern, demonstrating their identical origin. The two lines, however, have different DNA methylation patterns. The multipotent germline stem cells formed chimeras after blastocyst injection but did not produce sperm after germ cell transplantation, whereas the germline stem cells could produce only spermatozoa and did not differentiate into somatic cells. interestingly, the germline stem cells expressed several transcription factors (Pou5f1, Sox2, Myc, and KIf4) required for reprogramming fibroblasts into a pluripotent state, suggesting that they are potentially pluripotent. Thus, our study provides evidence that a single spermatogonial stem cell can acquire pluripotentiality but that conversion into a pluripotent cell type is accompanied by loss of spermatogenic potential.