| Project/Area Number |
18K14605
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 42030:Animal life science-related
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 卵母細胞 / トランスクリプトーム / MGA / DIOLs / ダイレクトリプログラミング / 減数分裂 / エピゲノムリプログラミング / 遺伝子ネットワーク / in vitro oogenesis / 転写ネットワーク / RNA-seq / 卵子 / Transcriptional network / Totipotency / Oogenesis / In vitro oogenesis / Germ cell development |
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| Outline of Final Research Achievements |
In the mammalian germ line, oocytes acquire a unique cell state with a characteristically large cytoplasm, yet the molecular mechanism triggering the acquisition is unknown. Here we defined a key transcriptional network that orchestrates the formation of oocytes in mice. Transcriptome analysis of the entire cycle of the germline revealed a huge transcriptional transition named maternal genome activation (MGA), where germ cells acquire the oocytic transcriptome. We identified eight transcription factors that were each essential for MGA. Strikingly, upon expression of these factors, pluripotent stem cells formed oocyte-like cells with a potency for fertilization by sperm. These directly induced oocyte-like cells were formed without passing through PGC specification, epigenetic reprogramming, or meiosis. This study illustrates the distinct molecular switch initiating oocyte formation, which is an essential process for the preparation of the totipotent state during germline development.
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| Academic Significance and Societal Importance of the Research Achievements |
iPS細胞に代表されるように、細胞を転写因子によって直接転換する方法はこれまでに様々な細胞種に応用され、医療応用に向けて研究開発が進んでいる。しかし何百種類以上ある細胞の中でもイレギュラーな存在である卵母細胞へと直接転換する方法はこれまでに樹立されてこなかった。今回申請者らはマウスES/iPS細胞に遺伝子導入を行い、卵母細胞へと直接転換する方法を確立した。この方法では数十日かかる卵母細胞発生ステージまでたった数日で到達した。本研究により、卵母細胞形成に必要な遺伝子セットが明らかになっただけではなく、将来的な臨床応用への障壁となりうる培養の長期化を打破しうるツールを得たと言えるだろう。
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