Inter-cellular RNA transfer-driven reprogramming
| Project/Area Number |
19K22416
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Takebe Takanori 東京医科歯科大学, 統合研究機構, 教授 (20612625)
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| Project Period (FY) |
2019-06-28 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Keywords | 細胞間相互作用 / リプログラミング / mRNA / ナイーブ型 |
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| Outline of Research at the Start |
われわれは、マウス細胞とヒト細胞とを特定条件下で培養を行うことにより、マウスmRNAがヒト細胞に受け渡されていることを見出した。本研究では、われわれが世界で初めて発見した異なる細胞種間の直接接触を介したmRNAの伝搬機構の解明を通じて、細胞の運命を転換するための全く新たな細胞操作技術を構築する。今後、遺伝子編集を伴わない安全かつ安定な細胞を創出できるばかりか、未解明な細胞間相互作用に関わるさまざまな生命現象、例えば、正常幹細胞とニッチ間相互作用、ガンと間質間の相互作用など 、近年着目されている多細胞間相互作用に関する研究を全く新たな視点から切り込むための基盤原理へと昇華する可能性がある。
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| Outline of Final Research Achievements |
Working with the experimental model of xenogenic cell co-culture, we recently found the striking phenomenon of bidirectional mRNA exchange between human and mouse cells. This led us to hypothesize that the transferred mRNAs influence the landscape both of transcriptome and epigenome in neighboring cell counterpart. To test this, we set up the co-culture system of human iPS cells and mouse ES cells as an experimental model and revealed the followings in this study. 1) Some portion of RNAs are transferred from mouse ES cells into human iPS cells primarily driven by direct cell-to-cell contact; 2) After the RNA transfer, human iPS cells can covert from primed to naive-like states; 3) Among mouse ES cell-derived RNAs, specific mRNAs coding transcription factors are responsible for human iPS cell conversion into naive-like states.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によって見いだされた、細胞間mRNA転送というメカニズムは新規の生命現象であり、本現象が免疫系細胞との相互作用、ニッチ環境との相互作用などを始め、さまざまな正常の生命現象において重要な意義を担う可能性も想定される。実際、免疫系を中心に生体内でも類似の知見が徐々に報告されつつあることから、将来的にさまざまな疾患研究への可能性がある。将来的には、がんなどの疾患における細胞間相互作用を理解するための全く新たな原理基盤の提唱にもつながり、革新的な創薬研究への発展が期待される。
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Report
(3 results)
Research Products
(70 results)
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[Journal Article] High-Fidelity Drug-Induced Liver Injury Screen Using Human Pluripotent Stem Cell?Derived Organoids2021
Author(s)
Shinozawa T, Kimura M, Cai Y, Saiki N, Yoneyama Y, Ouchi R, Koike H, Maezawa M, Zhang RR, Dunn A, Ferguson A, Togo S, Lewis K, Thompson WL, Asai A, Takebe T.
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Journal Title
Gastroenterology
Volume: 160
Issue: 3
Pages: 831-846.e10
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Simultaneous Zn2+ tracking in multiple organelles using super-resolution morphology-correlated organelle identification in living cells2021
Author(s)
Fang H, Geng S, Hao M, Chen Q, Liu M, Liu C, Tian Z, Wang C, Takebe T, Guan JL, Chen Y, Guo Z, He W, Diao J.
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Journal Title
Nature Communications
Volume: 12
Issue: 1
Pages: 109-109
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Modeling Human Bile Acid Transport and Synthesis in Stem Cell-Derived Hepatocytes with a Patient-Specific Mutation2021
Author(s)
Hayashi H, Osaka S, Sakabe K, Fukami A, Kishimoto E, Aihara E, Sabu Y, Mizutani A, Kusuhara H, Naritaka N, Zhang W, Huppert SS, Sakabe M, Nakamura T, Hu YC, Mayhew C, Setchell K, Takebe T, Asai A.
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Journal Title
Stem Cell Reports
Volume: 16
Issue: 2
Pages: 309-323
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection2021
Author(s)
Dobrindt K, Hoagland DA, Seah C, Kassim B, OShea CP, Murphy A, Iskhakova M, Fernando MB, Powell SK, Deans PJM, Javidfar B, Peter C, Muller R, Uhl SA, Garcia MF, Kimura M, Iwasawa K, Crary JF, Kotton DN, Takebe T, Huckins LM, tenOever BR, Akbarian S, Brennand KJ.
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Journal Title
Stem Cell Reports
Volume: 16
Issue: 3
Pages: 505-518
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Voices of biotech research2021
Author(s)
Annabi N, ..., Takebe T, Vandenberghe LH, Varshney RK, Wang J.
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Journal Title
Nature Biotechnology
Volume: 39
Issue: 3
Pages: 281-286
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis.2020
Author(s)
Han L, Chaturvedi P, Kishimoto K, Koike H, Nasr T, Iwasawa K, Giesbrecht K, Witcher PC, Eicher A, Haines L, Lee Y, Shannon JM, Morimoto M, Wells JM, Takebe T, Zorn AM.
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Journal Title
Nature communications
Volume: 11(1)
Issue: 1
Pages: 4158-4158
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Polygenic architecture informs potential vulnerability to drug-induced liver injury2020
Author(s)
Koido M, Kawakami E, Fukumura J, Noguchi Y, Ohori M, Nio Y, Nicoletti P, Aithal GP, Daly AK, Watkins PB, Anayama H, Dragan Y, Shinozawa T, Takebe T.
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Journal Title
Nature Medicine
Volume: 26
Issue: 10
Pages: 1541-1548
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Generation of human induced pluripotent stem cell-derived liver buds with chemically defined and animal origin-free media2020
Author(s)
Sekine K, Ogawa S, Tsuzuki S, Kobayashi T, Ikeda K, Nakanishi N, Takeuchi K, Kanai E, Otake Y, Okamoto S, Kobayashi T, Takebe T, Taniguchi H.
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Journal Title
Scientific Reports
Volume: 10
Issue: 1
Pages: 17937-17937
DOI
Related Report
Peer Reviewed / Open Access
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