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タイトル: | GATA transcription factors, SOX17 and TFAP2C, drive the human germ-cell specification program |
著者: | Kojima, Yoji Yamashiro, Chika Murase, Yusuke Yabuta, Yukihiro Okamoto, Ikuhiro https://orcid.org/0000-0002-2870-8321 (unconfirmed) Iwatani, Chizuru Tsuchiya, Hideaki Nakaya, Masataka Tsukiyama, Tomoyuki Nakamura, Tomonori https://orcid.org/0000-0002-0173-0780 (unconfirmed) Yamamoto, Takuya https://orcid.org/0000-0002-0022-3947 (unconfirmed) Saitou, Mitinori |
著者名の別形: | 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 |
発行日: | May-2021 |
出版者: | Life Science Alliance, LLC |
誌名: | Life Science Alliance |
巻: | 4 |
号: | 5 |
論文番号: | e202000974 |
抄録: | 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. |
記述: | 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. |
著作権等: | © 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(出版社版): | 10.26508/lsa.202000974 |
PubMed ID: | 33608411 |
関連リンク: | https://ashbi.kyoto-u.ac.jp/ja/news/20210219_research-result_saitou/ https://ashbi.kyoto-u.ac.jp/news/20210219_research-result_saitou/ |
出現コレクション: | 学術雑誌掲載論文等 |
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