Testicular endothelial cells are a critical population in the germline stem cell niche

• Published in: Nature communications Vol. 9; no. 1; pp. 4379 - 16
• Main Authors: Bhang, Dong Ha, Kim, Bang-Jin, Kim, Byung Gak, Schadler, Keri, Baek, Kwan-Hyuck, Kim, Yong Hee, Hsiao, Wayland, Ding, Bi-Sen, Rafii, Shahin, Weiss, Mitchell J., Chou, Stella T., Kolon, Thomas F., Ginsberg, Jill P., Ryu, Buom-Yong, Ryeom, Sandra
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.10.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/100; 13/106; 59; 631/532/2139; 631/80/86/1999; 64; Animals; Apoptosis - drug effects; Calcineurin; Cancer; Cell culture; Cell Line; Cell Proliferation - drug effects; Cell self-renewal; Chemotherapy; Cytotoxicity; Endothelial cells; Endothelial Cells - cytology; Endothelial Cells - drug effects; Fertility; Fertility Preservation; Fibroblast growth factor 2; Fibroblast growth factor receptor 1; Germ Cells; Glial cell line-derived neurotrophic factor; Glial Cell Line-Derived Neurotrophic Factor - pharmacology; Hepatocytes; Humanities and Social Sciences; Humans; Liver; Lungs; Male; Mice; multidisciplinary; Neuronal-glial interactions; Preservation; Science; Science (multidisciplinary); Secretome; Spermatogenesis; Spermatogenesis - drug effects; Stem Cell Niche - drug effects; Stem cell transplantation; Stem cells; Testes; Testis - cytology; Transplantation
• ISSN: 2041-1723; 2041-1723
• 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. 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.