| Autor: |
Huadie Liu, Ye Liu, Seung-Gi Jin, Jennifer Johnson, Hongwen Xuan, Di Lu, Jianshuang Li, Lukai Zhai, Xianfeng Li, Yaguang Zhao, Minmin Liu, Sonya E.L. Craig, Joseph S. Floramo, Vladimir Molchanov, Jie Li, Jia-Da Li, Connie Krawczyk, Xiaobing Shi, Gerd P. Pfeifer, Tao Yang |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 42, Iss 1, Pp 112012- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2023.112012 |
| Popis: |
Summary: Long bones are generated by mesoderm-derived skeletal progenitor/stem cells (SSCs) through endochondral ossification, a process of sequential chondrogenic and osteogenic differentiation tightly controlled by the synergy between intrinsic and microenvironment cues. Here, we report that loss of TRIM28, a transcriptional corepressor, in mesoderm-derived cells expands the SSC pool, weakens SSC osteochondrogenic potential, and endows SSCs with properties of ectoderm-derived neural crest cells (NCCs), leading to severe defects of skeletogenesis. TRIM28 preferentially enhances H3K9 trimethylation and DNA methylation on chromatin regions more accessible in NCCs; loss of this silencing upregulates neural gene expression and enhances neurogenic potential. Moreover, TRIM28 loss causes hyperexpression of GREM1, which is an extracellular signaling factor promoting SSC self-renewal and SSC neurogenic potential by activating AKT/mTORC1 signaling. Our results suggest that TRIM28-mediated chromatin silencing establishes a barrier for maintaining the SSC lineage trajectory and preventing a transition to ectodermal fate by regulating both intrinsic and microenvironment cues. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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