Short C-terminal Musashi-1 proteins regulate pluripotency states in embryonic stem cells

Youwei Chen; Ying Chen; Qianyan Li; Huahua Liu; Jiazhen Han; Hailin Zhang; Liming Cheng; Gufa Lin

doi:10.1016/j.celrep.2023.113308

Short C-terminal Musashi-1 proteins regulate pluripotency states in embryonic stem cells

Cell Rep. 2023 Oct 31;42(10):113308. doi: 10.1016/j.celrep.2023.113308. Epub 2023 Oct 19.

Authors

Youwei Chen¹, Ying Chen², Qianyan Li², Huahua Liu², Jiazhen Han², Hailin Zhang², Liming Cheng³, Gufa Lin⁴

Affiliations

¹ 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 University, Shanghai, China; Clinical Center for Brain and Spinal Cord Research, Medical School, Tongji University, Shanghai, China.
² 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 University, Shanghai, China.
³ 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 University, Shanghai, China; Clinical Center for Brain and Spinal Cord Research, Medical School, Tongji University, Shanghai, China. Electronic address: limingcheng@tongji.edu.cn.
⁴ 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 University, Shanghai, China; Clinical Center for Brain and Spinal Cord Research, Medical School, Tongji University, Shanghai, China. Electronic address: lingufa@tongji.edu.cn.

PMID: 37858462
DOI: 10.1016/j.celrep.2023.113308

Abstract

The RNA-binding protein Musashi-1 (MSI1) regulates the proliferation and differentiation of adult stem cells. However, its role in embryonic stem cells (ESCs) and early embryonic development remains poorly understood. Here, we report the presence of short C-terminal MSI1 (MSI1-C) proteins in early mouse embryos and mouse ESCs, but not in human ESCs, under conventional culture conditions. In mouse embryos and mESCs, deletion of MSI1-C together with full-length MSI1 causes early embryonic developmental arrest and pluripotency dissolution. MSI1-C is induced upon naive induction and facilitates hESC naive pluripotency acquisition, elevating the pluripotency of primed hESCs toward a formative-like state. MSI1-C proteins are nuclear localized and bind to RNAs involved in DNA-damage repair (including MLH1, BRCA1, and MSH2), conferring on hESCs better survival in human-mouse interspecies cell competition and prolonged ability to form blastoids. This study identifies MSI1-C as an essential regulator in ESC pluripotency states and early embryonic development.

Keywords: CP: Stem cell research; DNA-damage repair; MSI1-C; Musashi-1; cell competition; embryonic stem cells; naive; pluripotency state; primed.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Embryonic Stem Cells* / metabolism
Human Embryonic Stem Cells* / metabolism
Humans
Mice
Mouse Embryonic Stem Cells / metabolism
Nerve Tissue Proteins / metabolism
RNA / metabolism
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism

Substances

MSI1 protein, human
Nerve Tissue Proteins
RNA
RNA-Binding Proteins
Msi1h protein, mouse