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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 22 OCT 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 11, pages 2412–2422, November 2012
How to Cite
Hoxha, E., Lambers, E., Xie, H., De Andrade, A., Krishnamurthy, P., Wasserstrom, J. A., Ramirez, V., Thal, M., Verma, S. K., Soares, M. B. and Kishore, R. (2012), Histone Deacetylase 1 Deficiency Impairs Differentiation and Electrophysiological Properties of Cardiomyocytes Derived from Induced Pluripotent Cells. STEM CELLS, 30: 2412–2422. doi: 10.1002/stem.1209
Author contributions: E.H.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; E.M.L.: manuscript writing; V.R., M.A.T., S.K.V., P.K., and M.B.S.: conception and design; H.X., A.D.A., and J.A.W.: collection and/or assembly of data; R.K.: conception and design, final editing, and approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS August 22, 2012.
- Issue published online: 22 OCT 2012
- Article first published online: 22 OCT 2012
- Accepted manuscript online: 22 AUG 2012 08:36AM EST
- Manuscript Accepted: 24 JUL 2012
- Manuscript Received: 6 JUN 2012
- National Institute of Health. Grant Numbers: HL091983, HL105597, HL095874, HL053354, HL108795
- American Heart Association's predoctoral fellowship. Grant Number: 11PRE7360065
- Stem cells;
- Induced pluripotent stem cells;
- Epigenetic regulation;
- Histone deacetylases;
- Histone deacetylase 1;
- Cardiovascular differentiation
Epigenetic and chromatin modifications play particularly important roles in embryonic and induced pluripotent stem cells (ESCs and iPSCs) allowing for the cells to both differentiate and dedifferentiate back to a pluripotent state. We analyzed how the loss of a key chromatin-modifying enzyme, histone deacetylase 1 (HDAC1), affects early and cardiovascular differentiation of both ESCs and iPSCs. We also investigated potential differences between these two cell types when differentiation is induced. Our data indicate an essential role for HDAC1 in deacetylating regulatory regions of key pluripotency-associated genes during early differentiation. Although HDAC1 functions primarily as a HDAC, its loss also affects DNA methylation in ESCs and iPSCs both during pluripotency and differentiation. We show that HDAC1 plays a crucial, nonredundant role in cardiomyocyte differentiation and maturation. Our data also elucidate important differences between ESCs and iPSCs, when levels of this enzyme are reduced, that affect their ability to differentiate into functional cardiomyocytes. As varying levels of chromatin-modifying enzymes are likely to exist in patient-derived iPSCs, understanding the molecular circuitry of these enzymes in ESCs and iPSCs is critical for their potential use in cardiovascular therapeutic applications. STEM CELLS2012;30:2412–2422