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BMC Genomics. 2015 Aug 20;16:624. doi: 10.1186/s12864-015-1833-5.

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

Author information

1
Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan.
2
Research Institute for Disease of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
3
Department of Histology and Cell Biology, Yokohama City University School of Medicine, Yokohama, 236-0004, Japan.
4
NODAI Genome Research Center, Tokyo University of Agriculture, Tokyo, 156-8502, Japan.
5
Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan.
6
Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, 236-0004, Japan.
7
Division of Genomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan.
8
Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwanoha 5-1-5, Kashiwa, Chiba, 277-8568, Japan.
9
Department of BioScience, Tokyo University of Agriculture, Tokyo, 156-8502, Japan.
10
Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan. hsasaki@bioreg.kyushu-u.ac.jp.

Abstract

BACKGROUND:

In 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.

RESULTS:

To 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.

CONCLUSIONS:

Our 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.

PMID:
26290333
PMCID:
PMC4546090
DOI:
10.1186/s12864-015-1833-5
[Indexed for MEDLINE]
Free PMC Article

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