![]() ![]() However, all current heart repair strategies have been focused on regeneration of heart muscle without subtype specification. Thus, significant loss or dysfunction of individual cardiac subtypes can lead to specific forms of potentially life-threatening heart disease depending upon the identity of the affected cell type. ![]() Highly coordinated activity of all three cardiac subtypes is required for effective blood pumping. ![]() There are three major types of cardiomyocytes in the heart as defined by anatomical location and unique electrical properties: atrial, ventricular, and pacemaker. Over the last four years, we have taken three fundamental steps toward this goal: 1) in vitro reprogramming of adult mouse fibroblasts into beating cardiomyocytes by forced expression of four transcription factors, 2) developing in vivo reprogramming strategy targeting activated cardiac fibroblasts after myocardial infarction, which improved heart function and reduced scar formation, and 3) identifying the optimal combination of factors that is necessary and sufficient to induce a contractile phenotype in adult human fibroblasts. ![]() Therefore, to convert cardiac fibroblasts, the most abundant cell type in the heart, into cardiomyocytes after injury is a particularly attractive heart repair strategy. A fundamental, but unsolved problem in heart diseases is irreversible loss of cardiomyocytes that is replaced by fibrotic scar in response to injury. ![]()
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