Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA, 19104, USA.
Department of Molecular and Cellular Biology, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi 440-746, Korea.
Nat Commun. 2018 Oct 22;9(1):4379. doi: 10.1038/s41467-018-06881-z.
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.
成人组织的维持依赖于局部龛位中的干细胞自我更新。精原干细胞（SSC）是生殖系成体干细胞，对于精子发生和生育能力是必需的。我们表明，睾丸内皮细胞（TEC）是 SSC 龛位的一部分，可产生胶质细胞系衍生的神经营养因子（GDNF）和其他因子，以支持人源和鼠源 SSC 在长期培养中生长。我们证明，TEC 上的 FGF-2 与 FGFR1 结合可激活钙调神经磷酸酶途径产生 GDNF。将 TEC 分泌组与肺和肝内皮细胞进行比较，鉴定出 5 种因子，它们足以在无饲养细胞的培养中维持人源和鼠源 SSC 集落的长期生长。接受化疗的男性癌症幸存者通常不育，因为 SSC 对细胞毒性损伤非常敏感。在化疗诱导的 SSC 耗竭后，单独移植 TEC 可恢复小鼠的精子发生。将 TEC 鉴定为 SSC 自我更新所必需的龛位群体，可能有助于为诊断患有癌症的青春期前男孩保存生育能力。
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