Abstract 1450: Temporal Gene Expression Profiling of Human-Derived Cardiomyocyte Progenitor Cells during Cardiomyocyte Differentiation
Myocardial regeneration can occur in humans, albeit with very low efficiency. To improve regeneration of the injured myocardium, the intrinsic capacity of the heart to replace damaged tissue should be enhanced. Recently, we have isolated cardiomyocyte progenitor cells (CMPCs) from human fetal hearts and from adult human biopsies that can be expanded in culture and efficiently differentiated into beating cardiomyocytes, providing us with a model to study cardiomyogenesis. To improve our understanding of how cardiac predetermination and differentiation is regulated we analyzed the gene expression during CMPC differentiation.
Methods and results: Human fetal CMPCs were isolated, cultured, and stimulated with 5-azacytidine and TGF-beta to induce efficient cardiomyogenic differentiation. mRNA samples were prepared at 0, 1, 2, and 3 weeks after the initiation of differentiation and hybridized on whole-genome expression beadchips (Refseq 8, Illumina). At three weeks of differentiation human CMPC demonstrated spontaneous beating. Using the PANTHER Classification System, we showed that the genes expressed by undifferentiated CMPCs were mainly involved in signal transduction, developmental processes and protein metabolism. At 3 weeks, the differentiated CMPCs expressed genes that regulate cell structure, immunity and mesoderm/muscle formation. Currently, we are analyzing the temporal expression of interesting target genes that are involved in the initiation and progression of differentiation since these genes might enhance the intrinsic regenerative capacity of the heart, and test their role in muscle differentiation.
Conclusion: Human-derived CMPCs can efficiently been differentiated into cardiomyocytes and is a useful human model to improve our understanding of cardiac muscle differentiation.