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

Author

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  • Dong Ha Bhang

    (Perelman School of Medicine at the University of Pennsylvania
    Sungkyunkwan University School of Medicine
    Sungkyunkwan University School of Medicine)

  • Bang-Jin Kim

    (Perelman School of Medicine at the University of Pennsylvania)

  • Byung Gak Kim

    (Perelman School of Medicine at the University of Pennsylvania
    Sungkyunkwan University School of Medicine)

  • Keri Schadler

    (Perelman School of Medicine at the University of Pennsylvania
    The University of Texas MD Anderson Cancer Center)

  • 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)

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.

Suggested Citation

  • 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, 2018. "Testicular endothelial cells are a critical population in the germline stem cell niche," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06881-z
    DOI: 10.1038/s41467-018-06881-z
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