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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, etc.

Nat Commun. 2018 Oct 22;9(1):4379.

PMID: 30348976

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR4248825 GDNF from mouse GDNF from mouse Price
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