論文

査読有り 国際誌
2021年5月

GATA transcription factors, SOX17 and TFAP2C, drive the human germ-cell specification program.

Life science alliance
  • Yoji Kojima
  • ,
  • Chika Yamashiro
  • ,
  • Yusuke Murase
  • ,
  • Yukihiro Yabuta
  • ,
  • Ikuhiro Okamoto
  • ,
  • Chizuru Iwatani
  • ,
  • Hideaki Tsuchiya
  • ,
  • Masataka Nakaya
  • ,
  • Tomoyuki Tsukiyama
  • ,
  • Tomonori Nakamura
  • ,
  • Takuya Yamamoto
  • ,
  • Mitinori Saitou

4
5
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.26508/lsa.202000974

The in vitro reconstitution of human germ-cell development provides a robust framework for clarifying key underlying mechanisms. Here, we explored transcription factors (TFs) that engender the germ-cell fate in their pluripotent precursors. Unexpectedly, SOX17, TFAP2C, and BLIMP1, which act under the BMP signaling and are indispensable for human primordial germ-cell-like cell (hPGCLC) specification, failed to induce hPGCLCs. In contrast, GATA3 or GATA2, immediate BMP effectors, combined with SOX17 and TFAP2C, generated hPGCLCs. GATA3/GATA2 knockouts dose-dependently impaired BMP-induced hPGCLC specification, whereas GATA3/GATA2 expression remained unaffected in SOX17, TFAP2C, or BLIMP1 knockouts. In cynomolgus monkeys, a key model for human development, GATA3, SOX17, and TFAP2C were co-expressed exclusively in early PGCs. Crucially, the TF-induced hPGCLCs acquired a hallmark of bona fide hPGCs to undergo epigenetic reprogramming and mature into oogonia/gonocytes in xenogeneic reconstituted ovaries. By uncovering a TF circuitry driving the germ line program, our study provides a paradigm for TF-based human gametogenesis.

リンク情報
DOI
https://doi.org/10.26508/lsa.202000974
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33608411
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918644
ID情報
  • DOI : 10.26508/lsa.202000974
  • PubMed ID : 33608411
  • PubMed Central 記事ID : PMC7918644

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