Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes
Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes
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成年大鼠睾丸曲细精管相关干间质细胞的调节
DOI：
10.1073/pnas.1519395113
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发表时间：
2016-03-08
影响因子：
11.1
通讯作者：
Chen, Haolin
中科院分区：
文献类型：
--
作者：
Li, Xiaoheng;Wang, Zhao;Chen, Haolin
睾丸间质细胞是男性睾酮的主要来源。成人间质细胞已被证明是由新生儿睾丸中的干细胞产生的。一旦建立，成年Leydig细胞在成年生活中仅缓慢翻转，但当这些细胞从成年睾丸中实验性地消除时，新的Leydig细胞迅速重新出现。与新生儿睾丸一样，成人睾丸中的干细胞被认为是新Leydig细胞的来源。到目前为止，参与调节这些干细胞增殖和分化的机制仍然未知。我们开发了一种独特的体外培养生精小管系统，以评估生精小管因子调节小管相关干细胞增殖及其随后进入Leydig细胞谱系的能力。旁分泌因子包括沙漠刺猬（DHH）、碱性成纤维细胞生长因子（FGF 2）、血小板源性生长因子（PDGF）和激活素，可以刺激干间质细胞的增殖。转化生长因子β（TGF-β）可抑制增殖。干细胞的分化受到DHH、锂诱导信号和激活素的正向调节，受到TGF-β、PDGFBB和FGF 2的负向调节。DHH作为一种定型因子，诱导干细胞向祖细胞阶段过渡，从而进入Leydig细胞谱系。此外，发现CD 90（Thy 1）是用于通过流式细胞术获得纯化的干细胞的独特的干细胞表面标志物。
Testicular Leydig cells are the primary source of testosterone in males. Adult Leydig cells have been shown to arise from stem cells present in the neonatal testis. Once established, adult Leydig cells turn over only slowly during adult life, but when these cells are eliminated experimentally from the adult testis, new Leydig cells rapidly reappear. As in the neonatal testis, stem cells in the adult testis are presumed to be the source of the new Leydig cells. As yet, the mechanisms involved in regulating the proliferation and differentiation of these stem cells remain unknown. We developed a unique in vitro system of cultured seminiferous tubules to assess the ability of factors from the seminiferous tubules to regulate the proliferation of the tubule-associated stem cells, and their subsequent entry into the Leydig cell lineage. The proliferation of the stem Leydig cells was stimulated by paracrine factors including Desert hedgehog (DHH), basic fibroblast growth factor (FGF2), platelet-derived growth factor (PDGF), and activin. Suppression of proliferation occurred with transforming growth factor beta (TGF-beta). The differentiation of the stem cells was regulated positively by DHH, lithium-induced signaling, and activin, and negatively by TGF-beta, PDGFBB, and FGF2. DHH functioned as a commitment factor, inducing the transition of stem cells to the progenitor stage and thus into the Leydig cell lineage. Additionally, CD90 (Thy1) was found to be a unique stem cell surface marker that was used to obtain purified stem cells by flow cytometry.