In vitro expansion of mouse primordial germ cell-like cells recapitulates an epigenetic blank slate

Hiroshi Ohta, Kazuki Kurimoto, Ikuhiro Okamoto, Tomonori Nakamura, Yukihiro Yabuta, Hidetaka Miyauchi, Takuya Yamamoto, Yukiko Okuno, Masatoshi Hagiwara, Kenjiro Shirane, Hiroyuki Sasaki, Mitinori Saitou

研究成果: Contribution to journalArticle

28 引用 (Scopus)

抜粋

The expansion of primordial germ cells (PGCs), the precursors for the oocytes and spermatozoa, is a key challenge in reproductive biology/medicine. Using a chemical screening exploiting PGC-like cells (PGCLCs) induced from mouse embryonic stem cells (ESCs), we here identify key signaling pathways critical for PGCLC proliferation. We show that the combinatorial application of Forskolin and Rolipram, which stimulate cAMP signaling via different mechanisms, expands PGCLCs up to ~50-fold in culture. The expanded PGCLCs maintain robust capacity for spermatogenesis, rescuing the fertility of infertile mice. Strikingly, during expansion, PGCLCs comprehensively erase their DNA methylome, including parental imprints, in a manner that precisely recapitulates genome-wide DNA demethylation in gonadal germ cells, while essentially maintaining their identity as sexually uncommitted PGCs, apparently through appropriate histone modifications. By establishing a paradigm for PGCLC expansion, our system reconstitutes the epigenetic “blank slate” of the germ line, an immediate precursory state for sexually dimorphic differentiation.

元の言語英語
ページ(範囲)1888-1907
ページ数20
ジャーナルEMBO Journal
36
発行部数13
DOI
出版物ステータス出版済み - 7 3 2017

All Science Journal Classification (ASJC) codes

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

フィンガープリント In vitro expansion of mouse primordial germ cell-like cells recapitulates an epigenetic blank slate' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用

    Ohta, H., Kurimoto, K., Okamoto, I., Nakamura, T., Yabuta, Y., Miyauchi, H., Yamamoto, T., Okuno, Y., Hagiwara, M., Shirane, K., Sasaki, H., & Saitou, M. (2017). In vitro expansion of mouse primordial germ cell-like cells recapitulates an epigenetic blank slate. EMBO Journal, 36(13), 1888-1907. https://doi.org/10.15252/embj.201695862