Oscillations of MyoD and Hes1 proteins regulate the maintenance of activated muscle stem cells.
Hes1
MyoD
muscle stem cell
ultradian oscillation
Journal
Genes & development
ISSN: 1549-5477
Titre abrégé: Genes Dev
Pays: United States
ID NLM: 8711660
Informations de publication
Date de publication:
01 05 2019
01 05 2019
Historique:
received:
20
11
2018
accepted:
19
02
2019
pubmed:
14
3
2019
medline:
2
7
2019
entrez:
14
3
2019
Statut:
ppublish
Résumé
The balance between proliferation and differentiation of muscle stem cells is tightly controlled, ensuring the maintenance of a cellular pool needed for muscle growth and repair. We demonstrate here that the transcriptional regulator Hes1 controls the balance between proliferation and differentiation of activated muscle stem cells in both developing and regenerating muscle. We observed that Hes1 is expressed in an oscillatory manner in activated stem cells where it drives the oscillatory expression of MyoD. MyoD expression oscillates in activated muscle stem cells from postnatal and adult muscle under various conditions: when the stem cells are dispersed in culture, when they remain associated with single muscle fibers, or when they reside in muscle biopsies. Unstable MyoD oscillations and long periods of sustained MyoD expression are observed in differentiating cells. Ablation of the Hes1 oscillator in stem cells interfered with stable MyoD oscillations and led to prolonged periods of sustained MyoD expression, resulting in increased differentiation propensity. This interfered with the maintenance of activated muscle stem cells, and impaired muscle growth and repair. We conclude that oscillatory MyoD expression allows the cells to remain in an undifferentiated and proliferative state and is required for amplification of the activated stem cell pool.
Identifiants
pubmed: 30862660
pii: gad.322818.118
doi: 10.1101/gad.322818.118
pmc: PMC6499323
doi:
Substances chimiques
MyoD Protein
0
Receptors, Notch
0
Transcription Factor HES-1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
524-535Informations de copyright
© 2019 Lahmann et al.; Published by Cold Spring Harbor Laboratory Press.
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