Testicular endothelial cells are a critical population in the germline stem cell niche.
Testicular endothelial cells are a critical population in the germline stem cell niche.
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DOI：
10.1038/s41467-018-06881-z
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发表时间：
2018-10-22
影响因子：
16.6
通讯作者：
Ryeom S
中科院分区：
文献类型：
--
作者：
Bhang DH;Kim BJ;Kim BG;Schadler K;Baek KH;Kim YH;Hsiao W;Ding BS;Rafii S;Weiss MJ;Chou ST;Kolon TF;Ginsberg JP;Ryu BY;Ryeom S
成体组织的维持依赖于干细胞在局部小生境中的自我更新。精原干细胞（spermatogonialstemcells，SSC）是精子发生和生育所必需的生殖系成体干细胞。我们发现，睾丸内皮细胞（TEC）是SSC生态位的一部分，产生胶质细胞源性神经营养因子（GDNF）和其他因子，以支持人类和小鼠SSC的长期培养。我们证明FGF-2与TEC上的FGFR 1结合激活钙调磷酸酶途径以产生GDNF。TEC分泌组与肺和肝内皮细胞的比较确定了足以在无饲养层培养物中长期维持人和小鼠SSC集落的5个因素。化疗后的男性癌症幸存者通常不育，因为SSC对细胞毒性损伤高度敏感。在化疗诱导的精原干细胞耗竭后，单独移植TEC可恢复小鼠的精子发生。将TEC确定为SSC自我更新所需的小生境人群可能有助于青春期前诊断患有癌症的男孩的生育力保护。精原干细胞（SSC）的自我更新是精子发生和男性生育所必需的。在这里，作者将睾丸内皮细胞（TEC）确定为人类和小鼠SSC自我更新和扩增的5种关键生长因子的来源。
Maintenance of adult tissues depends on stem cell self-renewal in local niches. Spermatogonial stem cells (SSC) are germline adult stem cells necessary for spermatogenesis and fertility. We show that testicular endothelial cells (TECs) are part of the SSC niche producing glial cell line-derived neurotrophic factor (GDNF) and other factors to support human and mouse SSCs in long-term culture. We demonstrate that FGF-2 binding to FGFR1 on TECs activates the calcineurin pathway to produce GDNF. Comparison of the TEC secretome to lung and liver endothelial cells identified 5 factors sufficient for long-term maintenance of human and mouse SSC colonies in feeder-free cultures. Male cancer survivors after chemotherapy are often infertile since SSCs are highly susceptible to cytotoxic injury. Transplantation of TECs alone restores spermatogenesis in mice after chemotherapy-induced depletion of SSCs. Identifying TECs as a niche population necessary for SSC self-renewal may facilitate fertility preservation for prepubertal boys diagnosed with cancer. Self-renewal of spermatogonial stem cells (SSC) is necessary for spermatogenesis and male fertility. Here the authors identify testicular endothelial cells (TECs) as a source of 5 key growth factors for self-renewal and expansion of human and mouse SSCs.
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影响因子：
23.9
作者：
Butler JM;Nolan DJ;Vertes EL;Varnum-Finney B;Kobayashi H;Hooper AT;Seandel M;Shido K;White IA;Kobayashi M;Witte L;May C;Shawber C;Kimura Y;Kitajewski J;Rosenwaks Z;Bernstein ID;Rafii S
通讯作者：
Rafii S
影响因子：
8.5
作者：
Lim, J. J.;Sung, S. -Y.;Lee, D. R.
通讯作者：
Lee, D. R.
影响因子：
3.2
作者：
Meistrich, Marvin L.
通讯作者：
Meistrich, Marvin L.
影响因子：
4.1
作者：
Hofmann, Marie-Claude
通讯作者：
Hofmann, Marie-Claude
影响因子：
6.1
作者：
Davisson, M.;Akeson, E.;Handel, M. A.
通讯作者：
Handel, M. A.