Intercellular mRNA transfer alters the human pluripotent stem cell state

• 成果类型: Article
• 署名作者: Yoneyama, Yosuke; Zhang, Ran-Ran; Maezawa, Mari; Masaki, Hideki; Kimura, Masaki; Cai, Yuqi; Adam, Mike; Parameswaran, Sreeja; Mizuno, Naoaki; Bhadury, Joydeep; Maezawa, So; Ochiai, Hiroshi; Nakauchi, Hiromitsu; Potter, S. Steven; Weirauch, Matthew T.; Takebe, Takanori
• 署名单位: University of Osaka; Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; Stanford University; Tokyo University of Science; Kyushu University; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14824
• DOI: 10.1073/pnas.2413351122
• 发表日期: 2025-01-28
• 关键词: tunneling nanotubes; somatic-cells; human naive; fibroblasts; micrornas; nuclei; mouse

摘要

Intercellular transmission of messenger RNA (mRNA) is being explored in mammalian species using immortal cell lines. Here, we uncover an intercellular mRNA transfer phenomenon that allows for the adaptation and reprogramming of human primed pluripotent stem cells (hPSCs). This process is induced by the direct cell contact- mediated coculture with mouse embryonic stem cells under the condition impermissible for primed hPSC culture. Mouse- derived mRNA contents are transmitted into adapted hPSCs only in the coculture. Transfer- specific mRNA analysis shows the enrichment for divergent biological pathways involving transcription/translational machinery and stress- coping mechanisms, wherein such transfer is diminished when direct cell contacts are lost. After 5 d of coculture with mouse embryonic stem cells, surface marker analysis and global gene profiling confirmed that knockdown experiments targeting mouse- specific transcription factor- coding mRNAs in in mammalian cells. Our results support that episodic mRNA transfer can occur in cell cooperative and competitive processes, which provides a fresh perspective on understanding the roles of mRNA mobility for intra- and interspecies cellular communications.