Abstract 14925: CHF1/Hey2 is Required for Cardiomyocyte Derivation from Mouse Embryonic Stem Cells
Generating cardiomyocytes from pluripotent cells for use in cardiac repair is a promising area of research in the treatment of chronic cardiovascular diseases. In order to develop precise methods for cardiomyocyte generation we must understand the factors involved in cardiomyocyte development and maturation. CHF1/Hey2 is a bHLH transcription factor involved in normal mouse cardiac development and its absence leads to ventricular septal defects as well as a thin-walled ventricle. We have further demonstrated that CHF1 suppresses atrial gene expression in the developing ventricle. Therefore we hypothesized that CHF1 would be required for the differentiation of ventricular cardiomyocytes. We tested this hypothesis using a mouse embryonic stem (mES) cell model. Here we demonstrate that during differentiation of mES cells into cardiomyocytes through a directed differentiation protocol, CHF1 is expressed in a time dependent manner following cardiac progenitor formation. We knocked down CHF1 using shRNA during differentiation by 75% and found that differentiating cells were unable to proliferate and survive. Importantly scrambled shRNA did not alter the differentiation of mES cells into cardiomyocytes or CHF1 levels. Furthermore we overexpressed CHF1 following mesoderm induction through lentiviral transduction and demonstrate that this results in a 20% increase in yield of cardiomyocytes. We conclude that CHF1 is required for the differentiation of mES cells into cardiomyocytes and the function of CHF1 may be related to early myocyte cell survival and proliferation.
- © 2012 by American Heart Association, Inc.