Open AccessNotch Signaling Is Necessary to Maintain Quiescence in Adult Muscle Stem Cells
Author(s) -
Bjornson Christopher R.R.,
Cheung Tom H.,
Liu Ling,
Tripathi Pinky V.,
Steeper Katherine M.,
Rando Thomas A.
Publication year - 2012
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.773
Subject(s) - biology , notch signaling pathway , myogenesis , microbiology and biotechnology , stem cell , transcription factor , skeletal muscle , signal transduction , myocyte , cellular differentiation , anatomy , genetics , gene
Satellite cells (SCs) are myogenic stem cells found in skeletal muscle that function to repair tissue damaged by injury or disease. SCs are quiescent at rest, although the signaling pathways required to maintain quiescence are unknown. Using a transgenic Notch reporter mouse and quantitative reverse‐transcription polymerase chain reaction analysis of Notch target genes, we determined that Notch signaling is active in quiescent SCs. SC‐specific deletion of recombining binding protein‐Jκ (RBP‐Jκ), a nuclear factor required for Notch signaling, resulted in the depletion of the SC pool and muscles that lacked any ability to regenerate in response to injury. SC depletion was not due to apoptosis. Rather, RBP‐Jκ‐deficient SCs spontaneously activate, fail to self‐renew, and undergo terminal differentiation. Intriguingly, most of the cells differentiate without first dividing. They then fuse with adjacent myofibers, leading to the gradual disappearance of SCs from the muscle. These results demonstrate the requirement of Notch signaling for the maintenance of the quiescent state and for muscle stem cell homeostasis by the regulation of self‐renewal and differentiation, processes that are all critical for normal postnatal myogenesis. S TEM C ELLS 2012; 30:232–242.