講演情報
[III-IL5-1]Cellular Reprogramming as a Basis for Heart Disease
○Deepak Srivastava1 (Gladstone Institutes and University of California, San Francisco)
Heart disease is a leading cause of death in adults and children. We, and others, have described complex signaling, transcriptional and translational networks that guide early differentiation of cardiac progenitors and later morphogenetic events during cardiogenesis. By leveraging these networks, we have reprogrammed disease-specific human cells to iPS cells in order to model genetically defined human heart disease in patients carrying mutations in cardiac developmental genes. These studies revealed mechanisms of disease, which often involve endogenous reprogramming of cells to alternative fates that underlie the disease process. We also utilized a combination of major cardiac developmental regulatory factors to induce direct reprogramming of resident cardiac fibroblasts into cardiomyocyte-like cells with global gene expression and electrical activity similar to cardiomyocytes, and have revealed the epigenetic mechanisms underlying the cell fate switch. Knowledge regarding the early steps of cardiac differentiation in vivo has led to effective strategies to generate necessary cardiac cell types for disease-modeling and regenerative approaches, and may lead to new strategies for human heart disease.