한빛사 논문
Seung-Jun Lee1,†, Jinah Park2,†, Dong-Joon Lee1, Keishi Otsu3, Pyunggang Kim2,4, Seiya Mizuno5, Min-Jung Lee1, Hyun-Yi Kim1, Hidemitsu Harada3, Satoru Takahashi5, Seong-Jin Kim2,6,7,*, Han-Sung Jung1,*
1Division in Anatomy and Developmental Biology, Department of Oral Biology, Taste Research Center, Oral Science Research Center, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul 03722, Korea
2Precision Medicine Research Center, Advanced Institute of Convergence Technology, Seoul National University, Suwon, Gyeonggi-do 16229, Korea
3Division of Developmental Biology & Regenerative Medicine, Department of Anatomy, Iwate Medical University School of Dentistry, Iwate 028-3694, Japan
4Department of Biomedical Science, College of Life Science, CHA University, Seongnam, Gyeonggi-do 463-400, Korea
5Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
6Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Suwon, Gyeonggi-do 16229, Korea
7Medpacto Inc., Seoul 03722, Korea
†These authors contributed equally: Seung-Jun Lee, Jinah Park
*Correspondence to Seong-Jin Kim or Han-Sung Jung.
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.
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