Mef2c/p300 Promotes Maturation of Induced Cardiomyocytes

Cardiac transcription factors (TFs) directly reprogram fibroblasts into induced cardiomyocytes (iCMs), where Mef2c acts as a pioneer factor with Gata4 and Tbx5 (GT). However, generation of functional and mature iCMs is inefficient and molecular mechanisms underlying this process remains largely unknown. Here we found that transduction of transcriptionally activated Mef2c via fusion of the powerful MyoD transactivation domain increased generation of beating iCMs by 30-fold in combination with GT. MEFs were transduced with the retrovirus (Gata4, Mef2cM2, Mef2c_TAD, Tbx5) mixtures as indicated. Cells were collected after 4 weeks. Hearts were harvested E12.5 and 8 weeks old for bulk RNA-seq.