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.

Details

Title
Testicular endothelial cells are a critical population in the germline stem cell niche
Author
Dong Ha Bhang 1 ; Bang-Jin, Kim 2 ; Kim, Byung Gak 3 ; Schadler, Keri 4 ; Kwan-Hyuck Baek 5   VIAFID ORCID Logo  ; Kim, Yong Hee 6 ; Hsiao, Wayland 7 ; Bi-Sen, Ding 7 ; Rafii, Shahin 7 ; Weiss, Mitchell J 8 ; Chou, Stella T 9 ; Kolon, Thomas F 10 ; Ginsberg, Jill P 11 ; Buom-Yong Ryu 6   VIAFID ORCID Logo  ; Ryeom, Sandra 2 

1  Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Molecular and Cellular Biology, Sungkyunkwan University School of Medicine, Suwon, Korea; BK21Plus Program for 21st Century Biomedical Science Leader Development, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi 440-746, Korea 
2  Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA 
3  Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Molecular and Cellular Biology, Sungkyunkwan University School of Medicine, Suwon, Korea 
4  Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
5  Department of Molecular and Cellular Biology, Sungkyunkwan University School of Medicine, Suwon, Korea 
6  Department of Animal Science and Technology, Chung-Ang University, Ansung, Korea 
7  Ansary Stem Cell Institute, Howard Hughes Medical Institute, Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, USA 
8  Department of Hematology, St. Jude Children’s Research Hospital, Memphis, TN, USA 
9  Division of Hematology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA 
10  Division of Urology, Children’s Hospital of Philadelphia, Department of Surgery (Urology), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA 
11  Division of Oncology, Children’s Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania,, Philadelphia, PA, USA 
Pages
1-16
Publication year
2018
Publication date
Oct 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-06881-z
ProQuest document ID
2124122069
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.