Sall4 and Gata4 Induce Cardiac Fibroblast Transition Towards a Partially Multipotent State with Cardiogenic Potential

Cardiac cellular fate transition holds remarkable promise for the treatment of ischemic heart disease. We report that overexpressing two transcription factors, Sall4 and Gata4, which play distinct and overlapping roles in both pluripotent stem cell reprogramming and embryonic heart development, induces a fraction of stem-like cells in rodent cardiac fibroblasts that develop unlimited ex vivo expandability with clonogenicity. Under suitable conditions, these expanding cells demonstrate a high susceptibility to differentiating into various cardiovascular cell types. RNA-Seq was conducted to elucidate the gene expression profiles in these cells with and without specific differentiation. Four groups of cells were designed: GS cell (undifferentiated), GS diff1 (treated with CMM medium), GS diff2 (treated with CMM medium plus EGM2 solution), and untreated parental rat cardiac fibroblasts, which served as controls.Three biological replicates were investigated for each group