Regulation of ES Cell Cardiac Differentiation by PRC1 Complexes

Extensive effort has been focused on applying stem cell-based therapy to treat cardiovascular diseases, the leading cause of human death. However, the lack of comprehensive understanding of molecular mechanisms underlying cardiogenesis prevents us from harnessing the full potential of stem cell-based regeneration therapy. In addition to genetic pathways, epigenetic programs are greatly involved in the lineage specification during embryonic development of vertebrates, yet how they regulate cell identity is poorly understood. Recently, we discovered that a large family of protein complexes, namely Polycomb Repressive Complex 1 (PRC1), regulates diverse transcription programs via differential chromatin association. Previous reports by others have shown that certain PRC1 proteins are required for cardiac differentiation. Building on these studies we aim to uncover how mechanistically PRC1 complexes affect gene expression that is critical for the establishment and maintenance of cell identity during cardiac differentiation. In the present proposal, we will profile the dynamic changes of PRC1 complexes, and investigate their roles during cardiac differentiation through the combination of proteomic, biochemical and genomic studies. This investigation will provide important insights that likely facilitate the development of stem cell-based therapy for cardiovascular diseases. (AHA Program: Scientist Development Grant)