YY1 regulates skeletal muscle regeneration through controlling metabolic reprogramming of satellite cells
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AbstractSkeletal muscle satellite cells (SCs) are adult muscle stem cells responsible for muscle regeneration after acute or chronic injuries. The lineage progression of quiescent SC toward activation, proliferation, and differentiation during the regeneration is orchestrated by cascades of transcription factors (TFs). Here, we elucidate the function of TF Yin Yang1 (YY1) in muscle regeneration. Muscle-specific deletion of YY1 in embryonic muscle progenitors leads to severe deformity of diaphragm muscle formation, thus neonatal death. Inducible deletion of YY1 in SC almost completely blocks the acute damage-induced muscle repair and exacerbates the chronic injury-induced dystrophic phenotype. Examination of SC revealed that YY1 loss results in cell-autonomous defect in activation and proliferation. Mechanistic search revealed that YY1 binds and represses mitochondrial gene expression. Simultaneously, it also stabilizes Hif1α protein and activates Hif1α-mediated glycolytic genes to facilitate a metabolic reprogramming toward glycolysis which is needed for SC proliferation. Altogether, our findings have identified YY1 as a key regulator of SC metabolic reprogramming through its dual roles in modulating both mitochondrial and glycolytic pathways.
All Author(s) ListFengyuan Chen, Jiajian Zhou, Yuying Li, Yu Zhao, Jie Yuan, Yang Cao, Lijun Wang, Zongkang Zhang, Baoting Zhang, Chi Chiu Wang, Tom H Cheung, Zhenguo Wu, Carmen Chak‐Lui Wong, Hao Sun, Huating Wang
Journal nameEMBO Journal
Year2019
Month5
Volume Number38
Issue Number10
Article numbere99727
ISSN0261-4189
eISSN1460-2075
LanguagesEnglish-United Kingdom

Last updated on 2020-24-10 at 03:50