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c-JUN: a chromatin repressor that limits mesoderm differentiation in human pluripotent stem cells.

Authors :
Zhang R
Li G
Zhang Q
Wang Z
Xiang D
Zhang X
Chen J
Hutchins AP
Qin D
Su H
Pei D
Li D
Source :
Nucleic acids research [Nucleic Acids Res] 2025 Jan 24; Vol. 53 (3).
Publication Year :
2025

Abstract

Cell fate determination at the chromatin level is not fully comprehended. Here, we report that c-JUN acts on chromatin loci to limit mesoderm cell fate specification as cells exit pluripotency. Although c-JUN is widely expressed across various cell types in early embryogenesis, it is not essential for maintaining pluripotency. Instead, it functions as a repressor to constrain mesoderm development while having a negligible impact on ectoderm differentiation. c-JUN interacts with MBD3-NuRD complex, which helps maintain chromatin in a low accessibility state at mesoderm-related genes during the differentiation of human pluripotent stem cells into mesoderm. Furthermore, c-JUN specifically inhibits the activation of key mesoderm factors, such as EOMES and GATA4. Knocking out c-JUN or inhibiting it with a JNK inhibitor can alleviate this suppression, promoting mesoderm cell differentiation. Consistently, knockdown of MBD3 enhances mesoderm generation, whereas MBD3 overexpression impedes it. Overexpressing c-JUN redirects differentiation toward a fibroblast-like lineage. Collectively, our findings suggest that c-JUN acts as a chromatin regulator to restrict the mesoderm cell fate.<br /> (© The Author(s) 2025. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Details

Language :
English
ISSN :
1362-4962
Volume :
53
Issue :
3
Database :
MEDLINE
Journal :
Nucleic acids research
Publication Type :
Academic Journal
Accession number :
39876710
Full Text :
https://doi.org/10.1093/nar/gkaf001