Journal
JOURNAL OF CELL SCIENCE
Volume 125, Issue 24, Pages 6009-6019Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.109546
Keywords
Satellite cells; Skeletal muscle; Yes-associated protein (Yap); Hippo pathway
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Funding
- Oliver Bird PhD studentship
- Medical Research Council [99477]
- Tenovus Scotland [G11/05]
- Canadian Institutes of Health Research (CIHR)
- Wellcome Trust [085137/Z/08/Z]
- Raine Medical Research Foundation
- National Institutes of Health [NIH-P50-NS40828, NIH-P30-HD18655]
- Medical Research Council [G1100193] Funding Source: researchfish
- Wellcome Trust [085137/Z/08/Z] Funding Source: Wellcome Trust
- MRC [G1100193] Funding Source: UKRI
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Satellite cells are the resident stem cells of skeletal muscle. Mitotically quiescent in mature muscle, they can be activated to proliferate and generate myoblasts to supply further myonuclei to hypertrophying or regenerating muscle fibres, or self-renew to maintain the resident stem cell pool. Here, we identify the transcriptional co-factor Yap as a novel regulator of satellite cell fate decisions. Yap expression increases during satellite cell activation and Yap remains highly expressed until after the differentiation versus self-renewal decision is made. Constitutive expression of Yap maintains Pax7(+) and MyoD(+) satellite cells and satellite cell-derived myoblasts, promotes proliferation but prevents differentiation. In contrast, Yap knockdown reduces the proliferation of satellite cell-derived myoblasts by approximate to 40%. Consistent with the cellular phenotype, microarrays show that Yap increases expression of genes associated with Yap inhibition, the cell cycle, ribosome biogenesis and that it represses several genes associated with angiotensin signalling. We also identify known regulators of satellite cell function such as BMP4, CD34 and Myf6 (Mrf4) as genes whose expression is dependent on Yap activity. Finally, we confirm in myoblasts that Yap binds to Tead transcription factors and co-activates MCAT elements which are enriched in the proximal promoters of Yap-responsive genes.
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