Stiff matrix induces switch to pure β-cardiac myosin heavy chain expression in human ESC-derived cardiomyocytes.

摘要: Human pluripotent stem cell (hPSC)-derived cardiomyocytes hold great potential for in vitro modeling of diseases like cardiomyopathies. Yet, knowledge about expression and functional impact sarcomeric protein isoforms the myosin heavy chain (MyHC) hPSC-cardiomyocytes is scarce. We hypothesized that ventricular β-MyHC alters contraction calcium kinetics drives morphological electrophysiological differentiation towards ventricular-like cardiomyocytes. To address this, we (1) generated human embryonic cell-derived (hESC-CMs) switched exclusive β-MyHC, (2) functionally morphologically characterized these hESC-CMs at single-cell level. MyHC-isoforms properties were investigated during prolonged culture floating cardiac bodies (soft conditions) vs. on a stiff matrix. Using specific anti-β-MyHC newly anti-α-MyHC-antibody, found individual grown to mostly express both α- β-MyHC-protein isoforms. 35 75 days cultivation laminin-coated glass 66 87 % all exclusively respectively. Twitch transients faster CMs laminin-glass. Surprisingly, parameters only little affected by MyHC-isoform, although with had much lower ATP-turnover tension cost, just as Spontaneous contractions no strict coupling action potentials suggest MyHC-isoform does not fully determine hESC-CM status. Stiff substrate-induced pure hESC-CMs, several contractile close cardiomyocytes, provides well-defined system cardiomyopathies drug screening approaches.