The present invention relates to endogenous cardiac stem-progenitor cells (eCSCs). Provided herein are c-kitpos CD166pos eCSCs that are negative for the hematopoietic marker, CD45 and the mast cell marker, Tryptase. These single cell derived eCSCs can differentiate into a variety of specific cell types corresponding to the derivatives of the three germ layers. Also provided herein is a stage-specific TGF-P-Family/Wnt-Inhibitor cocktail for modulating in vitro myogenic specification and maturation of c-kitpos eCSCs. Also provided herein are methods of modulating eCSCs clonal expansion and differentiation. Also provided herein are screening assays for small organic molecules that modulate early cardiomyogenic progenitor cells. The invention further relates to the use of these modulated cells in prophylactic and therapeutic methods, including in pharmaceutical compositions of such cells, growth factors and/or small organic compounds. Finally, the invention relates to the use of such differentiated cells in transplantation and medical treatments.
