Bone morphogenetic protein and retinoic acid synergistically specify female germ-cell fate in mice

Hidetaka Miyauchi, Hiroshi Ohta, So Nagaoka, Fumio Nakaki, Kotaro Sasaki, Katsuhiko Hayashi, Yukihiro Yabuta, Tomonori Nakamura, Takuya Yamamoto, Mitinori Saitou

研究成果: ジャーナルへの寄稿記事

15 引用 (Scopus)

抄録

The mechanism for sex determination in mammalian germ cells remains unclear. Here, we reconstitute the female sex determination in mouse germ cells in vitro under a defined condition without the use of gonadal somatic cells. We show that retinoic acid (RA) and its key effector, STRA8, are not sufficient to induce the female germ-cell fate. In contrast, bone morphogenetic protein (BMP) and RA synergistically induce primordial germ cells (PGCs)/PGC-like cells (PGCLCs) derived from embryonic stem cells (ESCs) into fetal primary oocytes. The induction is characterized by entry into the meiotic prophase, occurs synchronously and recapitulates cytological and transcriptome progression in vivo faithfully. Importantly, the female germ-cell induction necessitates a proper cellular competence—most typically, DNA demethylation of relevant genes—which is observed in appropriately propagated PGCs/PGCLCs, but not in PGCs/PGCLCs immediately after induction. This provides an explanation for the differential function of BMP signaling between PGC specification and female germ-cell induction. Our findings represent a framework for a comprehensive delineation of the sex-determination pathway in mammalian germ cells, including humans.

元の言語英語
ページ(範囲)3100-3119
ページ数20
ジャーナルEMBO Journal
36
発行部数21
DOI
出版物ステータス出版済み - 11 2 2017

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Bone Morphogenetic Proteins
Tretinoin
Germ Cells
Cells
Stem cells
Specifications
DNA
Prophase
Embryonic Stem Cells
Transcriptome
Oocytes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

これを引用

Bone morphogenetic protein and retinoic acid synergistically specify female germ-cell fate in mice. / Miyauchi, Hidetaka; Ohta, Hiroshi; Nagaoka, So; Nakaki, Fumio; Sasaki, Kotaro; Hayashi, Katsuhiko; Yabuta, Yukihiro; Nakamura, Tomonori; Yamamoto, Takuya; Saitou, Mitinori.

:: EMBO Journal, 巻 36, 番号 21, 02.11.2017, p. 3100-3119.

研究成果: ジャーナルへの寄稿記事

Miyauchi, H, Ohta, H, Nagaoka, S, Nakaki, F, Sasaki, K, Hayashi, K, Yabuta, Y, Nakamura, T, Yamamoto, T & Saitou, M 2017, 'Bone morphogenetic protein and retinoic acid synergistically specify female germ-cell fate in mice', EMBO Journal, 巻. 36, 番号 21, pp. 3100-3119. https://doi.org/10.15252/embj.201796875
Miyauchi, Hidetaka ; Ohta, Hiroshi ; Nagaoka, So ; Nakaki, Fumio ; Sasaki, Kotaro ; Hayashi, Katsuhiko ; Yabuta, Yukihiro ; Nakamura, Tomonori ; Yamamoto, Takuya ; Saitou, Mitinori. / Bone morphogenetic protein and retinoic acid synergistically specify female germ-cell fate in mice. :: EMBO Journal. 2017 ; 巻 36, 番号 21. pp. 3100-3119.
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