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

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.

Nature communications. 2018 Oct 22*** epublish ***

Dong Ha Bhang, Bang-Jin Kim, Byung Gak Kim, Keri Schadler, Kwan-Hyuck Baek, Yong Hee Kim, Wayland Hsiao, Bi-Sen Ding, Shahin Rafii, Mitchell J Weiss, Stella T Chou, Thomas F Kolon, Jill P Ginsberg, Buom-Yong Ryu, Sandra Ryeom

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., Department of Animal Science and Technology, Chung-Ang University, Ansung, Gyeonggi-Do 456-756, Korea., Ansary Stem Cell Institute, Howard Hughes Medical Institute, Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA., Department of Hematology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA., Division of Hematology, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA, 19104, USA., Division of Urology, Children's Hospital of Philadelphia, Department of Surgery (Urology), Perelman School of Medicine at the University of Pennsylvania, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA., Division of Oncology, Children's Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania,, 3501 Civic Center Boulevard, Philadelphia, PA, 19104, USA., Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA, 19104, USA. .