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Zfp423 Regulates Skeletal Muscle Regeneration and Proliferation
- Source :
- Molecular and Cellular Biology
- Publication Year :
- 2018
-
Abstract
- Satellite cells (SCs) are skeletal muscle stem cells that proliferate in response to injury and provide myogenic precursors for growth and repair. Zfp423 is a transcriptional cofactor expressed in multiple immature cell populations, such as neuronal precursors, mesenchymal stem cells, and preadipocytes, where it regulates lineage allocation, proliferation, and differentiation.<br />Satellite cells (SCs) are skeletal muscle stem cells that proliferate in response to injury and provide myogenic precursors for growth and repair. Zfp423 is a transcriptional cofactor expressed in multiple immature cell populations, such as neuronal precursors, mesenchymal stem cells, and preadipocytes, where it regulates lineage allocation, proliferation, and differentiation. Here, we show that Zfp423 regulates myogenic progression during muscle regeneration. Zfp423 is undetectable in quiescent SCs but becomes expressed during SC activation. After expansion, Zfp423 is gradually downregulated as committed SCs terminally differentiate. Mice with satellite-cell-specific Zfp423 deletion exhibit severely impaired muscle regeneration following injury, with aberrant SC expansion, defective cell cycle exit, and failure to transition efficiently from the proliferative stage toward commitment. Consistent with a cell-autonomous role of Zfp423, shRNA-mediated knockdown of Zfp423 in myoblasts inhibits differentiation. Surprisingly, forced expression of Zfp423 in myoblasts induces differentiation into adipocytes and arrests myogenesis. Affinity purification of Zfp423 in myoblasts identified Satb2 as a nuclear partner of Zfp423 that cooperatively enhances Zfp423 transcriptional activity, which in turn affects myoblast differentiation. In conclusion, by controlling SC expansion and proliferation, Zfp423 is essential for muscle regeneration. Tight regulation of Zfp423 expression is essential for normal progression of muscle progenitors from proliferation to differentiation.
- Subjects :
- Satellite Cells, Skeletal Muscle
Muscle Fibers, Skeletal
Biology
Cell fate determination
Muscle Development
03 medical and health sciences
Mice
0302 clinical medicine
medicine
Adipocytes
Myocyte
Animals
Regeneration
Progenitor cell
Spotlight
skeletal muscle
Muscle, Skeletal
Molecular Biology
Cells, Cultured
030304 developmental biology
Cell Proliferation
Mice, Knockout
satellite cells
0303 health sciences
Wound Healing
cell fate
Myogenesis
Regeneration (biology)
Stem Cells
Mesenchymal stem cell
Skeletal muscle
Cell Differentiation
Mesenchymal Stem Cells
Cell Biology
Cell biology
DNA-Binding Proteins
Mice, Inbred C57BL
medicine.anatomical_structure
030220 oncology & carcinogenesis
myoblast
myogenesis
Stem cell
Signal Transduction
Transcription Factors
Research Article
Subjects
Details
- ISSN :
- 10985549
- Volume :
- 39
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Molecular and cellular biology
- Accession number :
- edsair.doi.dedup.....1e53d9dd5240f7d02906ece54c16ce44