Improved Factor Combination for In Vivo Reprogramming of Cardiac Myofibroblast to Cardiomyocyte-Like Cell With Dual Recombinase Tracing
Jingdong Wu, Hong Zhao, Yanmeng Tao, Chunyan Yang, Yang Yang, Bin Zhou, Yang Zhao
Abstract
onrenewable cell types such as cardiomyocytes die with injury and aging, causing irreversible damage to normal heart function.In vivo direct reprogramming can promote heart regeneration by converting proliferative, extracellular matrix-secreting activated cardiac myofibroblasts into cardiomyocytes.This approach replenishes cardiomyocytes while simultaneously ameliorating cardiac fibrosis.Previous studies have reported in vivo cardiac fibroblast reprogramming into cardiomyocytes through the expression of transcription factors (such as GATA4, MEF2C, TBX5 [GMT]), microRNA silencing, or transcription factor expression in conjunction with small molecule activators. 1 However, our previous study showed that activated myofibroblasts, the ideal targets of in vivo cardiac reprogramming, are more difficult to reprogram than resident cardiac fibroblasts in vitro. 2 The efficiency remains unclear of in vivo cardiac myofibroblast-to-cardiomyocyte-like cell reprogramming using stringent lineage tracing systems.Furthermore, the discovery of genetic and chemical boosters of in vitro myofibroblast-to-cardiomyocyte reprogramming 2 (Tao Y,