From fibroblast cells to cardiomyocytes: direct lineage reprogramming

Recent advances in stem cell biology have established the feasibility of reprogramming human and murine fibroblast cells into induced pluripotent stem cells. Three master regulators have been demonstrated to be sufficient in the management of cell status of 'pluripotent' versus 'differentiated'. The same strategy has been used to directly convert one somatic cell type into another cell type, such as the converting of exocrine pancreas cells into cells closely resembling beta cells and the reprogramming of fibroblast cells into functional neuron cells. Srivastava's group reported the first direct reprogramming of mouse fibroblast cells into mesoderm lineage cells (cardiomyocytes) with the enforced expression of three cardiac transcriptional factors: Gata4, Mef2c, and Tbx5. The induced cardiomyocytes exhibit a global gene expression profile and basic electrophysiological characteristics similar to those of postnatal cardiomyocytes. This study made significant advances in cardiovascular and stem cell fields and has important implications in understanding heart developmental biology as well as in potential therapies of human cardiovascular diseases.