Inter-cellular RNA transfer-driven reprogramming

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22416
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Takebe Takanori 東京医科歯科大学, 統合研究機構, 教授 (20612625)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 細胞間相互作用 / リプログラミング

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.

Free Research Field

発生生物学、幹細胞生物学、消化器内科学、再生医学

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。