CCAAT/enhancer-binding protein beta promotes muscle stem cell quiescence through regulation of quiescence-associated genes.
Stem Cells
; 39(3): 345-357, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33326659
ABSTRACT
Regeneration of skeletal muscle depends on resident muscle stem cells called satellite cells that in healthy, uninjured muscle remain quiescent (noncycling). After activation and expansion of satellite cells postinjury, satellite cell numbers return to uninjured levels and return to mitotic quiescence. Here, we show that the transcription factor CCAAT/enhancer-binding protein beta (C/EBPß) is required to maintain quiescence of satellite cells in uninjured muscle. We show that C/EBPß is expressed in quiescent satellite cells in vivo and upregulated in noncycling myoblasts in vitro. Loss of C/EBPß in satellite cells promotes their premature exit from quiescence resulting in spontaneous activation and differentiation of the stem cell pool. Forced expression of C/EBPß in myoblasts inhibits proliferation by upregulation of 28 quiescence-associated genes. Furthermore, we find that caveolin-1 is a direct transcriptional target of C/EBPß and is required for cell cycle exit in muscle satellite cells expressing C/EBPß. The induction of mitotic quiescence is considered necessary for the long-term maintenance of adult stem cell populations with dysregulation driving increased differentiation of progenitors and depletion of the stem cell pool. Our findings place C/EBPß as an important transcriptional regulator of muscle satellite cell quiescence.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regeneração
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Músculo Esquelético
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Fibras Musculares Esqueléticas
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Desenvolvimento Muscular
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Células Satélites de Músculo Esquelético
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Stem Cells
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Canadá