Visual Abstract - Cardiomyocyte Lineage Specification in Adult Human Cardiac Precursor Cells Via Modulation of Enhancer-Associated Long Noncoding RNA Expression: 10.1016/j.jacbts.2016.06.008

• Human CPCs produce predominantly smooth muscle cells.

• CPCs can be redirected to the cardiomyocyte fate by transient activation followed by inhibition of NOTCH signaling.

• Inhibition of NOTCH signaling during differentiation represses MIR-143/145 expression and blocks smooth muscle differentiation.

• Expression of the microRNAs is under control of CARMEN, a long noncoding RNA associated with an enhancer located in the MIR-143/145 locus and target of NOTCH signaling.

• The CARMEN/MIR-145/143 locus represents a promising therapeutic target to favor production of cardiomyocytes in cell replacement therapies.