Abstract 19912: Distinct Patterns of Histone Modifications at Promoters of Genes Expressed in Cardiomyocytes Between Cardiac Stem Cells and Mesenchymal Stem Cells
Introduction: Stem cell-based myocardial regeneration is a promising therapy for various heart diseases. Mesenchymal Stem Cells (MSCs) and Cardiac Stem cells (CSCs) possess different potentials to develop into cardiomyocytes. The mechanism underlying differentiation of MSCs and CSCs towards cardiomyocytes remains elusive. It is well established that histone modifications correlate with gene expression and contribute to cell plasticity and cell lineage commitment. Here we hypothesized that specific histone modifications accompany cardiomyocyte-specific gene expression, thus determining the differentiation capacities of MSCs and CSCs towards heart cells.
Methods: MSCs and CSCs were isolated from tibias and hearts of C57BL/6 mouse, respectively. Characteristics of MSCs and CSCs were identified by flow cytometry and mRNA-qPCR analysis. Chromatin immunoprecipitation (ChIP) followed by qPCR analysis was performed to determine histone modifications at the promoters of genes mainly expressed in cardiomyocytes.
Results: Flow cytometry analysis revealed that MSCs and CSCs expressed comparable levels of Sca-1, CD29, and CD44, hallmarks of stem cells. MSCs and CSCs proliferated at a similar rate. Notably, the genes encoding cardiac-specific transcription factors NKX2.5, Gata4, MEF2c and Tbx5 were transcribed at higher levels in CSCs, compared to MSCs. At the promoters of genes mainly expressed in cardiomyocytes (shown in graph), the levels of histone acetylation, as a mark indicative of gene activation, were higher in CSCs than those in MSCs.
Conclusion: Our data indicated that CSCs expressed the transcription factors required for acquisition of heart cell identity. Furthermore, there were higher levels of histone acetylation in CSCs, compared to those in MSCs, reflecting the strong potential of CSCs to develop into myocardiocytes.
- © 2010 by American Heart Association, Inc.