Other
19 Authors
- Xuan H,
- Li X,
- Liu Y,
- Liu M,
- Craig SEL,
- Molchanov V,
- Shi X,
- Liu H,
- Zhao Y,
- Zhai L,
- Li JD,
- Johnson J,
- Yang T,
- Pfeifer GP,
- Floramo JS,
- Jin SG,
- Krawczyk C,
- Lu D,
- Li J
| First Author | Liu H | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 1 | Pages | 112012 |
| PubMed ID | 36680774 | Mgi Jnum | J:333040 |
| Mgi Id | MGI:7432241 | Doi | 10.1016/j.celrep.2023.112012 |
| Citation | Liu H, et al. (2023) TRIM28 secures skeletal stem cell fate during skeletogenesis by silencing neural gene expression and repressing GREM1/AKT/mTOR signaling axis. Cell Rep 42(1):112012 |
| abstractText | 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. |
