Perturb-seq uncovers pathological obstacles to direct cardiac reprogramming in vivo - PubMed
4 hours ago
- #Cardiac Reprogramming
- #Calreticulin
- #Perturb-seq
- Direct induction of cardiomyocytes from fibroblasts is a promising cardiac regeneration strategy, but in vivo efficiency remains low.
- Using Perturb-seq in pathological environments, researchers identified calreticulin (Calr) as a top inhibitor of in vivo cardiac reprogramming among 140 potential barriers.
- Calr knockdown enhanced induced cardiomyocyte (iCM) induction efficiency in vitro, improved in situ reprogramming after myocardial infarction, and boosted cardiac function while reducing fibrosis.
- Mechanistically, Calr knockdown activates calcium signaling and increases MEF2C activity, driving reprogramming and potentially substituting for exogenous MEF2C.
- The study provides insights into regulators hindering in situ cardiomyocyte induction and offers a strategic framework for cardiac repair and regeneration post-myocardial infarction.