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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 25 OCT 2011
Copyright © 2011 AlphaMed Press
Volume 29, Issue 11, pages 1672–1683, November 2011
How to Cite
Rouleau, M., Medawar, A., Hamon, L., Shivtiel, S., Wolchinsky, Z., Zhou, H., De Rosa, L., Candi, E., de la Forest Divonne, S., Mikkola, M. L., van Bokhoven, H., Missero, C., Melino, G., Pucéat, M. and Aberdam, D. (2011), TAp63 Is Important for Cardiac Differentiation of Embryonic Stem Cells and Heart Development. STEM CELLS, 29: 1672–1683. doi: 10.1002/stem.723
Author contributions: M.R., M.P.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; A.M.: conception and design, collection and assembly of data, data analysis and interpretation, and final approval of manuscript; L.H., S.S., Z.W., H.Z., L.D.R., E.C., S.F.D, M.L.M., H.v.B., C.M., and G.M.: collection and assembly of data, final approval of manuscript; D.A.: conception and design, financial support, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript. Equal contribution to this article for M.R. and A.M., and for M.P. and D.A.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS September 2, 2011.
- Issue published online: 25 OCT 2011
- Article first published online: 25 OCT 2011
- Accepted manuscript online: 2 SEP 2011 12:05PM EST
- Manuscript Accepted: 13 AUG 2011
- Manuscript Received: 24 MAR 2011
- Sixth EEC Framework Program
- EPISTEM. Grant Number: LSHB-CT-2005-019067
- Agence Nationale pour la Recherche
- ANR BLANC 06, INSERM, and Israel Science Foundation
p63, a member of the p53 family, is essential for skin morphogenesis and epithelial stem cell maintenance. Here, we report an unexpected role of TAp63 in cardiogenesis. p63 null mice exhibit severe defects in embryonic cardiac development, including dilation of both ventricles, a defect in trabeculation and abnormal septation. This was accompanied by myofibrillar disarray, mitochondrial disorganization, and reduction in spontaneous calcium spikes. By the use of embryonic stem cells (ESCs), we show that TAp63 deficiency prevents expression of pivotal cardiac genes and production of cardiomyocytes. TAp63 is expressed by endodermal cells. Coculture of p63-knockdown ESCs with wild-type ESCs, supplementation with Activin A, or overexpression of GATA-6 rescue cardiogenesis. Therefore, TAp63 acts in a non-cell-autonomous manner by modulating expression of endodermal factors. Our findings uncover a critical role for p63 in cardiogenesis that could be related to human heart disease. STEM CELLS 2011;29:1672–1683