Judson RN, Tremblay AM, Knopp P, White RB, Urcia R, Bari CD, Zammit PS, Camargo FD, Wackerhage H
The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells.
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
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 <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.
Satellite cells, Skeletal muscle, Yes-associated protein (Yap), Hippo pathway
570 Biowissenschaften, Biologie; 610 Medizin und Gesundheit