DNA methylation and gene expression dynamics during spermatogonial stem cell differentiation in the early postnatal mouse testis

BMC Genomics

Research Article

Kazuyuki Ohbo¹  Takayuki Shirakawa¹  Shin-ichi Tomizawa¹  Yasuyuki Sato¹  Hidetoshi Sone¹  Naomichi Matsumoto²  Hirotomo Saitsu²  Yoshinori Tsurusaki²  Yutaka Suzuki³  Mikita Suyama⁴  Tetsuya Sato⁴  Kenjiro Shirane⁵  Hidehiro Toh⁵  Hiroyuki Sasaki⁵  Naoki Kubo⁶  Hiroki Shibata⁷  Hisato Kobayashi⁸  Tomohiro Kono⁹ 

[1] Department of Histology and Cell Biology, Yokohama City University School of Medicine, 236-0004, Yokohama, Japan;Department of Human Genetics, Graduate School of Medicine, Yokohama City University, 236-0004, Yokohama, Japan;Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwanoha 5-1-5, 277-8568, Kashiwa, Chiba, Japan;Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, 812-8582, Fukuoka, Japan;Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, 812-8582, Fukuoka, Japan;Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, 812-8582, Fukuoka, Japan;Research Institute for Disease of the Chest, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan;Division of Genomics, Medical Institute of Bioregulation, Kyushu University, 812-8582, Fukuoka, Japan;NODAI Genome Research Center, Tokyo University of Agriculture, 156-8502, Tokyo, Japan;NODAI Genome Research Center, Tokyo University of Agriculture, 156-8502, Tokyo, Japan;Department of BioScience, Tokyo University of Agriculture, 156-8502, Tokyo, Japan;

关键词: DNA methylation;    Non-CG methylation;    5-hydroxymethylcytosine;    Spermatogenesis;    Spermatogonial stem cell;    Prospermatogonia;    Spermatogonia;   

DOI  :  10.1186/s12864-015-1833-5

 received in 2015-04-09, accepted in 2015-08-07,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundIn the male germline, neonatal prospermatogonia give rise to spermatogonia, which include stem cell population (undifferentiated spermatogonia) that supports continuous spermatogenesis in adults. Although the levels of DNA methyltransferases change dynamically in the neonatal and early postnatal male germ cells, detailed genome-wide DNA methylation profiles of these cells during the stem cell formation and differentiation have not been reported.ResultsTo understand the regulation of spermatogonial stem cell formation and differentiation, we examined the DNA methylation and gene expression dynamics of male mouse germ cells at the critical stages: neonatal prospermatogonia, and early postntal (day 7) undifferentiated and differentiating spermatogonia. We found large partially methylated domains similar to those found in cancer cells and placenta in all these germ cells, and high levels of non-CG methylation and 5-hydroxymethylcytosines in neonatal prospermatogonia. Although the global CG methylation levels were stable in early postnatal male germ cells, and despite the reported scarcity of differential methylation in the adult spermatogonial stem cells, we identified many regions showing stage-specific differential methylation in and around genes important for stem cell function and spermatogenesis. These regions contained binding sites for specific transcription factors including the SOX family members.ConclusionsOur findings show a distinctive and dynamic regulation of DNA methylation during spermatogonial stem cell formation and differentiation in the neonatal and early postnatal testes. Furthermore, we revealed a unique accumulation and distribution of non-CG methylation and 5hmC marks in neonatal prospermatogonia. These findings contrast with the reported scarcity of differential methylation in adult spermatogonial stem cell differentiation and represent a unique phase of male germ cell development.

【 授权许可】

CC BY   
© Kubo et al. 2015