Document Detail


Constitutive Notch activation upregulates Pax7 and promotes the self-renewal of skeletal muscle satellite cells.
MedLine Citation:
PMID:  22493066     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Notch signaling is a conserved cell fate regulator during development and postnatal tissue regeneration. Using skeletal muscle satellite cells as a model and through myogenic cell lineage-specific NICD(OE) (overexpression of constitutively activated Notch 1 intracellular domain), here we investigate how Notch signaling regulates the cell fate choice of muscle stem cells. We show that in addition to inhibiting MyoD and myogenic differentiation, NICD(OE) upregulates Pax7 and promotes the self-renewal of satellite cell-derived primary myoblasts in culture. Using MyoD(-/-) myoblasts, we further show that NICD(OE) upregulates Pax7 independently of MyoD inhibition. In striking contrast to previous observations, NICD(OE) also inhibits S-phase entry and Ki67 expression and thus reduces the proliferation of primary myoblasts. Overexpression of canonical Notch target genes mimics the inhibitory effects of NICD(OE) on MyoD and Ki67 but not the stimulatory effect on Pax7. Instead, NICD regulates Pax7 through interaction with RBP-Jκ, which binds to two consensus sites upstream of the Pax7 gene. Importantly, satellite cell-specific NICD(OE) results in impaired regeneration of skeletal muscles along with increased Pax7(+) mononuclear cells. Our results establish a role of Notch signaling in actively promoting the self-renewal of muscle stem cells through direct regulation of Pax7.
Authors:
Yefei Wen; Pengpeng Bi; Weiyi Liu; Atsushi Asakura; Charles Keller; Shihuan Kuang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-04-09
Journal Detail:
Title:  Molecular and cellular biology     Volume:  32     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-24     Completed Date:  2013-02-21     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2300-11     Citation Subset:  IM    
Affiliation:
Department of Animal Sciences, Purdue University, West Lafayette, Indiana, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation
Cell Lineage
Cells, Cultured
Mice
Muscle Development / physiology
Muscle, Skeletal / cytology,  metabolism
PAX7 Transcription Factor / metabolism*
Protein Structure, Tertiary
Receptor, Notch1 / metabolism*
Satellite Cells, Skeletal Muscle* / cytology,  metabolism
Signal Transduction
Up-Regulation
Grant Support
ID/Acronym/Agency:
R01 AR060652/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Notch1 protein, mouse; 0/PAX7 Transcription Factor; 0/Pax7 protein, mouse; 0/Receptor, Notch1
Comments/Corrections

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