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Mast4 knockout shows the regulation of spermatogonial stem cell self-renewal via the FGF2/ERM pathway

Authors
 Seung-Jun Lee  ;  Jinah Park  ;  Dong-Joon Lee  ;  Keishi Otsu  ;  Pyunggang Kim  ;  Seiya Mizuno  ;  Min-Jung Lee  ;  Hyun-Yi Kim  ;  Hidemitsu Harada  ;  Satoru Takahashi  ;  Seong-Jin Kim  ;  Han-Sung Jung 
Citation
 CELL DEATH AND DIFFERENTIATION, Vol.28(5) : 1441-1454, 2021-05 
Journal Title
CELL DEATH AND DIFFERENTIATION
ISSN
 1350-9047 
Issue Date
2021-05
Abstract
Spermatogenesis is an important cellular differentiation process that produces the male gametes and remains active throughout the individual's lifespan. Sertoli cell-only syndrome (SCO) refers to the dysfunction of the male reproductive system, including infertility. Accurate self-renewal of spermatogonial stem cells (SSCs) is essential to prevent SCO syndrome. This study investigated the role of microtubule-associated serine/threonine kinase family member 4 (MAST4) in spermatogenesis in mice. MAST4 was localized in Sertoli cells before puberty, providing a somatic niche for spermatogenesis in mice and MAST4 expression shifted to Leydig cells and spermatids throughout puberty. Mast4 knockout (KO) testes were reduced in size compared to wild-type testes, and germ cell depletion associated with an increase in apoptosis and subsequent loss of tubular structure were similar to the SCO phenotype. In addition, MAST4 phosphorylated the Ets-related molecule (ERM), specifically the serine 367 residue. The phosphorylation of ERM ultimately controls the transcription of ERM target genes related to SSC self-renewal. The expression of spermatogenesis-associated proteins was significantly decreased whereas Sertoli cell markers were increased in Mast4 KO testes, which was well-founded by RNA-sequencing analysis. Therefore, MAST4 is associated with the fibroblast growth factor 2 (FGF2)/ERM pathway and this association helps us explore the capacity of SSCs to maintain a vertebrate stem cell niche.
Full Text
https://www.nature.com/articles/s41418-020-00670-2
DOI
10.1038/s41418-020-00670-2
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyun-Yi(김현이)
Jung, Han Sung(정한성) ORCID logo https://orcid.org/0000-0003-2795-531X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184008
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