Musashi1 and its short C-terminal variants regulate pluripotency states in embryonic stem cells
Musashi1 and its short C-terminal variants regulate pluripotency states in embryonic stem cells
ABSTRACT Musashi1 (MSI1) is a marker for adult stem cells, but little is known for its expression and function in pluripotent stem cells (PSCs). Here we report that MSI1 is expressed in embryonic stem cells (ESCs) and is required for pluripotency maintenance. We found that there exit short c-terminal MSI1 variants (MSI1-C, hMSI1272-362 or mMSI1138-362) in na?ve but not primed ESCs. When overexpressed, MSI1 and MSI1-C variants facilitate primed-to-na?ve pluripotency transition by elevating the pluripotency of primed hESCs toward a formative-like state, enable better survival of hESCs in human-mouse interspecies cell completion, and enhance the ability of blastoid formation of hESCs after na?ve induction. Mechanistically, we show that the MSI1-C variants, though lacking RNA recognition motifs, bind to RNAs, enhance stress resistance and upregulate DNA damage repair genes. Thus, this study demonstrates that ESCs utilize MSI1 and the newly identified short MSI1-C proteins as double swords to regulate pluripotency states.
Chen Youwei、Li Qianyan、Chen Ying、Lin Gufa、Zhang Hailin、Han Jiazhen
Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji University
分子生物学细胞生物学遗传学
Musashi1embryonic stem cellspluripotencyna?veprimedcell competitionstress responseDNA damage repair
Chen Youwei,Li Qianyan,Chen Ying,Lin Gufa,Zhang Hailin,Han Jiazhen.Musashi1 and its short C-terminal variants regulate pluripotency states in embryonic stem cells[EB/OL].(2025-03-28)[2025-05-13].https://www.biorxiv.org/content/10.1101/2022.05.02.490263.点此复制
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