Open AccessHistone Deacetylase 1 Deficiency Impairs Differentiation and Electrophysiological Properties of Cardiomyocytes Derived from Induced Pluripotent Cells
Author(s) -
Hoxha Eneda,
Lambers Erin,
Xie Hehuang,
De Andrade Alexandre,
Krishnamurthy Prasanna,
Wasserstrom John A.,
Ramirez Veronica,
Thal Melissa,
Verma Suresh K.,
Soares Marcelo B.,
Kishore Raj
Publication year - 2012
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1209
Subject(s) - biology , induced pluripotent stem cell , chromatin , microbiology and biotechnology , embryonic stem cell , epigenetics , cellular differentiation , histone deacetylase , histone , hdac1 , genetics , gene
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. S TEM C ELLS 2012;30:2412–2422