From stem cells to cardiomyocytes: the role of forces in cardiac maturation, aging, and disease.

Stem cell differentiation into a variety of lineages is known to involve signaling from the extracellular niche, including from the physical properties of that environment. What regulates stem cell responses to these cues is there ability to activate different mechanotransductive pathways. Here, we will review the structures and pathways that regulate stem cell commitment to a cardiomyocyte lineage, specifically examining proteins within muscle sarcomeres, costameres, and intercalated discs. Proteins within these structures stretch, inducing a change in their phosphorylated state or in their localization to initiate different signals. We will also put these changes in the context of stem cell differentiation into cardiomyocytes, their subsequent formation of the chambered heart, and explore negative signaling that occurs during disease.