Benjamin B Johnson, Marie-Victoire Cosson, Lorenza I Tsansizi, Terri L Holmes, Tegan Gilmore, Katherine Hampton, Ok-Ryul Song, Nguyen T N Vo, Aishah Nasir, Alzbeta Chabronova, Chris Denning, Mandy J Peffers, Catherine L R Merry, John Whitelock, Linda Troeberg, Stuart A Rushworth, Andreia S Bernardo, James G W Smith
Perlecan (HSPG2), a heparan sulfate proteoglycan similar to agrin, is key for extracellular matrix (ECM) maturation and stabilization. Although crucial for cardiac development, its role remains elusive. We show that perlecan expression increases as cardiomyocytes mature in vivo and during human pluripotent stem cell differentiation to cardiomyocytes (hPSC-CMs). Perlecan-haploinsuffient hPSCs (HSPG2+/- ) differentiate efficiently, but late-stage CMs have structural, contractile, metabolic, and ECM gene dysregulation...
January 9, 2024: Cell Reports