GSE98941
RNAseq of hPSC-derived cardiac progenitors: normal vs. polyI:C treated (functionally advanced), and TGFbeta treated (cardiac fibroblast progenitors)
Directed differentiation of human induced pluripotent stem cells creates billions of patient-specific cells. However, the differentiated derivatives of hiPS cells are immature relative to adult counterparts. Proliferative progenitor cells in these protocols are also therapeutically promising, but progenitors with enhanced potential for maturation have not been discovered. We hypothesized that brief epigenetic and innate immune modulation with polyinosinc cytidilic acid (pIC) could create cardiac progenitors with enhanced later maturation. Progenitor transcriptomic analysis revealed increases in cardiac crescent-like proliferative notch signaling by Jagged1, and activated progenitors spontaneously gave rise to cardiomyocytes with enhanced maturity and conductive microtissue with arrhythmogenic resistance. Furthermore, activated cardiac progenitors improved survival in animals after myocardial infarction compared to untreated progenitors. Our data suggest that future organization and maturation of cardiomyocytes are impacted by earlier pre-cardiomyocyte developmental signaling, and that progenitors modifying these pathways have translational promise. The forward epigenetic and immune modulation approach here utilized may be applicable to other cell lineages as well. Overall design: 9 samples total: 3 sample types (1 control/normal cardiac progenitors, vs. 2 groups of treated progenitors--with polyI:C or TGFbeta) x 3 biological reps.