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Title: GATA transcription factors, SOX17 and TFAP2C, drive the human germ-cell specification program
Authors: Kojima, Yoji
Yamashiro, Chika
Murase, Yusuke
Yabuta, Yukihiro
Okamoto, Ikuhiro  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-2870-8321 (unconfirmed)
Iwatani, Chizuru
Tsuchiya, Hideaki
Nakaya, Masataka
Tsukiyama, Tomoyuki
Nakamura, Tomonori  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-0173-0780 (unconfirmed)
Yamamoto, Takuya  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-0022-3947 (unconfirmed)
Saitou, Mitinori
Author's alias: 小島, 洋児
山城, 知佳
村瀬, 佑介
藪田, 幸宏
岡本, 郁弘
岩谷, 千鶴
土屋, 英明
中家, 雅隆
築山, 智之
中村, 友紀
山本, 拓也
斎藤, 通紀
Issue Date: May-2021
Publisher: Life Science Alliance, LLC
Journal title: Life Science Alliance
Volume: 4
Issue: 5
Thesis number: e202000974
Abstract: 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.
Description: ヒト生殖細胞の運命決定機序を解明 --転写因子のみによる生殖細胞の誘導. 京都大学プレスリリース. 2021-03-01.
Master regulator for human germ cell specification. 京都大学プレスリリース. 2021-03-01.
Rights: © 2021 Kojima et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
URI: http://hdl.handle.net/2433/261882
DOI(Published Version): 10.26508/lsa.202000974
PubMed ID: 33608411
Related Link: https://ashbi.kyoto-u.ac.jp/ja/news/20210219_research-result_saitou/
https://ashbi.kyoto-u.ac.jp/news/20210219_research-result_saitou/
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