A Molecular Switch Regulating the Cell Fate Choice Between Muscle Progenitor Cells and Brown Adipocytes
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AbstractDuring mouse embryo development, both muscle progenitor cells (MPCs) and brown adipocytes (BAs) are known to derive from the same Pax7+/Myf5+ progenitor cells. However, the underlying mechanisms for the cell fate control remain unclear. In Pax7-null MPCs from young mice, several BA-specific genes, including Prdm16 and Ucp1 and many other adipocyte-related genes, were upregulated with a concomitant reduction of Myod and Myf5, two muscle lineage-determining genes. This suggests a cell fate switch from MPC to BA. Consistently, freshly isolated Pax7-null but not wild-type MPCs formed lipid-droplet-containing UCP1+ BA in culture. Mechanistically, MyoD and Myf5, both known transcription targets of Pax7 in MPC, potently repress Prdm16, a BA-specific lineage-determining gene, via the E2F4/p107/p130 transcription repressor complex. Importantly, inducible Pax7 ablation in developing mouse embryos promoted brown fat development. Thus, the MyoD/Myf5-E2F4/p107/p130 axis functions in both the Pax7+/Myf5+ embryonic progenitor cells and postnatal myoblasts to repress the alternative BA fate.
All Author(s) ListYitai An, Gang Wang, Yarui Diao, Yanyang Long, Xinrong Fu, Mingxi Weng, Liang Zhou, Kun Sun, Tom H. Cheung, Nancy Y. Ip, Hao Sun, Huating Wang, Zhenguo Wu
Journal nameDevelopmental Cell
Volume Number41
Issue Number4
PublisherElsevier (Cell Press)
Pages382 - 391
LanguagesEnglish-United States
KeywordsE2F4/p107/p130, Myf5, MyoD, Pax7, Prdm16, Ucp1, brown adipocytes, cell fate control, muscle progenitor cells

Last updated on 2021-13-05 at 01:35