Abstract: Embodiments of the disclosure relate to methods and compositions for inducing maturation of cardiomyocytes. In some embodiments, the cardiomyocytes are derived from stem cells, in vitro. In some embodiments, the compositions and methods induce maturation by inducing overexpression of a Let7i microRNA (miRNA), overexpression of miR-452, reduced expression of miR-122, and/or reduced expression of miR-200a in the cardiomyocyte. In other embodiments, the disclosure relates to methods for treating conditions characterized by mitochondrial dysfunction, such as fatty acid oxidations disorders. In other embodiments, the disclosure relates to methods of screening for compounds that affect heart muscle function. In yet other embodiments, the disclosure relates to methods for detecting or monitoring mitochondrial dysfunction in a cell by detecting or monitoring the cardiolipin profile of the cell.

Abstract: The methods and compositions as disclosed herein describe the making of mature stem cell-derived cardiomyocytes for applications such as disease modeling, cardiotoxicity screening, drug screening and identification, among other uses. The methods involve physical and biochemical cues that promote a transition of stem cell-derived cardiomyocytes from a fetal phenotype to a more mature phenotype that more closely resembles that of adult cardiomyocytes.

Abstract: Provided herein are methods and compositions for maintaining human stem cells in either a nave state or a primed state, inducing, promoting, inhibiting, or controlling the transition from one state to another, and detecting the state of a stem cell. Also disclosed are compositions comprising substantially homogenous populations of primed state or nave state stem cells.