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

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 and Sandra Ryeom ()
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Dong Ha Bhang: Perelman School of Medicine at the University of Pennsylvania
Bang-Jin Kim: Perelman School of Medicine at the University of Pennsylvania
Byung Gak Kim: Perelman School of Medicine at the University of Pennsylvania
Keri Schadler: Perelman School of Medicine at the University of Pennsylvania
Kwan-Hyuck Baek: Sungkyunkwan University School of Medicine
Yong Hee Kim: Chung-Ang University
Wayland Hsiao: Weill Cornell Medical College
Bi-Sen Ding: Weill Cornell Medical College
Shahin Rafii: Weill Cornell Medical College
Mitchell J. Weiss: St. Jude Children’s Research Hospital
Stella T. Chou: The Children’s Hospital of Philadelphia
Thomas F. Kolon: Perelman School of Medicine at the University of Pennsylvania
Jill P. Ginsberg: Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania,
Buom-Yong Ryu: Chung-Ang University
Sandra Ryeom: Perelman School of Medicine at the University of Pennsylvania

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-06881-z

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