TY - JOUR
T1 - DNA methylation and gene expression dynamics during spermatogonial stem cell differentiation in the early postnatal mouse testis
AU - Kubo, Naoki
AU - Toh, Hidehiro
AU - Shirane, Kenjiro
AU - Shirakawa, Takayuki
AU - Kobayashi, Hisato
AU - Sato, Tetsuya
AU - Sone, Hidetoshi
AU - Sato, Yasuyuki
AU - Tomizawa, Shin Ichi
AU - Tsurusaki, Yoshinori
AU - Shibata, Hiroki
AU - Saitsu, Hirotomo
AU - Suzuki, Yutaka
AU - Matsumoto, Naomichi
AU - Suyama, Mikita
AU - Kono, Tomohiro
AU - Ohbo, Kazuyuki
AU - Sasaki, Hiroyuki
N1 - Funding Information:
We would like to thank Miho Miyake, Tomomi Akinaga, Junko Oishi (Kyushu University), Ikue Hoshi, Tamaki Nagasaka, Yoshito Kamizato, Nobuko Watanabe (Yokohama City University), Terumi Horiuchi (University of Tokyo), and Satoshi Sano (Tokyo University of Agriculture) for technical assistance and Illumina sequencing. We also thank Yoichi Nakanishi (Kyushu University) for generous support. K.S. is a Japan Society for the Promotion of Science (JSPS) research fellow. This work was supported in part by Grants-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science, and Technology of Japan to H. Sasaki (25112010), T.K. (22228004, 221S0002, and S0801025), and N.M. (24118007), and by the Core Research for Evolutional Science and Technology (CREST) from the Japan Agency for Medical Research and Development (AMED) to H. Sasaki. The work also received supports from a grant from AMED to N.M. (14525125) and the Kyushu University Interdisciplinary Programs in Education and Projects in Research Development (P&P) to H. Sasaki.
Publisher Copyright:
© 2015 Kubo et al.
PY - 2015/8/20
Y1 - 2015/8/20
N2 - 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.
AB - 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.
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U2 - 10.1186/s12864-015-1833-5
DO - 10.1186/s12864-015-1833-5
M3 - Article
C2 - 26290333
AN - SCOPUS:84939541148
SN - 1471-2164
VL - 16
JO - BMC genomics
JF - BMC genomics
IS - 1
M1 - 624
ER -
