The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells

Robert N. Judson, Annie M. Tremblay, Paul Knopp, Robert B. White, Roby Urcia, Cosimo De Bari, Peter S. Zammit, Fernando D. Camargo, Henning Wackerhage

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

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 ≈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.
Original languageEnglish
Pages (from-to)6009-6019
Number of pages11
JournalJournal of Cell Science
Volume125
Issue number24
Early online date4 Oct 2012
DOIs
Publication statusPublished - 15 Dec 2012

Fingerprint

Muscle Cells
Myoblasts
Stem Cells
Gene Expression
Muscles
Angiotensins
Ribosomes
Genes
Cell Cycle
Skeletal Muscle
Transcription Factors
Cell Proliferation
Phenotype

Keywords

  • satellite cells
  • skeletal muscle
  • yes-associated protein (yap)
  • hippo pathway

Cite this

Judson, R. N., Tremblay, A. M., Knopp, P., White, R. B., Urcia, R., De Bari, C., ... Wackerhage, H. (2012). The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells. Journal of Cell Science, 125(24), 6009-6019. https://doi.org/10.1242/jcs.109546

The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells. / Judson, Robert N.; Tremblay, Annie M.; Knopp, Paul; White, Robert B.; Urcia, Roby; De Bari, Cosimo; Zammit, Peter S.; Camargo, Fernando D.; Wackerhage, Henning.

In: Journal of Cell Science, Vol. 125, No. 24, 15.12.2012, p. 6009-6019.

Research output: Contribution to journalArticle

Judson, RN, Tremblay, AM, Knopp, P, White, RB, Urcia, R, De Bari, C, Zammit, PS, Camargo, FD & Wackerhage, H 2012, 'The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells' Journal of Cell Science, vol. 125, no. 24, pp. 6009-6019. https://doi.org/10.1242/jcs.109546
Judson, Robert N. ; Tremblay, Annie M. ; Knopp, Paul ; White, Robert B. ; Urcia, Roby ; De Bari, Cosimo ; Zammit, Peter S. ; Camargo, Fernando D. ; Wackerhage, Henning. / The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells. In: Journal of Cell Science. 2012 ; Vol. 125, No. 24. pp. 6009-6019.
@article{f0e3a2d7b86c48c284349db7aaef6653,
title = "The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells",
abstract = "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 ≈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.",
keywords = "satellite cells, skeletal muscle, yes-associated protein (yap), hippo pathway",
author = "Judson, {Robert N.} and Tremblay, {Annie M.} and Paul Knopp and White, {Robert B.} and Roby Urcia and {De Bari}, Cosimo and Zammit, {Peter S.} and Camargo, {Fernando D.} and Henning Wackerhage",
year = "2012",
month = "12",
day = "15",
doi = "10.1242/jcs.109546",
language = "English",
volume = "125",
pages = "6009--6019",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "24",

}

TY - JOUR

T1 - The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells

AU - Judson, Robert N.

AU - Tremblay, Annie M.

AU - Knopp, Paul

AU - White, Robert B.

AU - Urcia, Roby

AU - De Bari, Cosimo

AU - Zammit, Peter S.

AU - Camargo, Fernando D.

AU - Wackerhage, Henning

PY - 2012/12/15

Y1 - 2012/12/15

N2 - 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 ≈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.

AB - 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 ≈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.

KW - satellite cells

KW - skeletal muscle

KW - yes-associated protein (yap)

KW - hippo pathway

U2 - 10.1242/jcs.109546

DO - 10.1242/jcs.109546

M3 - Article

VL - 125

SP - 6009

EP - 6019

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 24

ER -