Li Xiaoheng, Wang Zhao, Jiang Zhenming, Guo Jingjing, Zhang Yuxi, Li Chenhao, Chung Jinyong, Folmer Janet, Liu June, Lian Qingquan, Ge Renshan, Zirkin Barry R, Chen Haolin
Center for Scientific Research, Institute of Reproductive Biomedicine, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China;
Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Jiamusi University, Jiamusi, Heilongjiang 154000, China;
Proc Natl Acad Sci U S A. 2016 Mar 8;113(10):2666-71. doi: 10.1073/pnas.1519395113. Epub 2016 Feb 29.
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 β (TGF-β). The differentiation of the stem cells was regulated positively by DHH, lithium- induced signaling, and activin, and negatively by TGF-β, 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.
睾丸间质细胞是男性睾酮的主要来源。已证实成年间质细胞起源于新生儿睾丸中的干细胞。一旦形成，成年间质细胞在成年期仅缓慢更新，但当通过实验从成年睾丸中清除这些细胞时，新的间质细胞会迅速重新出现。与新生儿睾丸一样，成年睾丸中的干细胞被认为是新间质细胞的来源。然而，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，以评估生精小管中的因子调节与小管相关的干细胞增殖以及它们随后进入间质细胞谱系的能力。旁分泌因子包括沙漠刺猬因子（DHH）、碱性成纤维细胞生长因子（FGF2）、血小板衍生生长因子（PDGF）和激活素可刺激间质干细胞的增殖。转化生长因子β（TGF-β）可抑制增殖。DHH、锂诱导的信号传导和激活素对干细胞的分化起正向调节作用，而TGF-β、PDGFBB和FGF2则起负向调节作用。DHH作为一种定向因子，诱导干细胞向祖细胞阶段转变，从而进入间质细胞谱系。此外，发现CD90（Thy1）是一种独特的干细胞表面标志物，可用于通过流式细胞术获得纯化的干细胞。
