HOPX-associated molecular programs control cardiomyocyte cell states underpinning cardiac structure and function

This study uses genetic loss-of-function human-induced pluripotent stem cell-derived cardiomyocytes to evaluate the genomic regulatory basis of the non-DNA-binding homeodomain protein HOPX. We show that HOPX interacts with and controls cardiac genes and enhancer networks associated with diverse aspects of heart development. Using perturbation studies in vitro, we define how upstream cell growth and proliferation control HOPX transcription to regulate cardiac gene programs. We then use cell, organoid, and zebrafish regeneration models to demonstrate that HOPX-regulated gene programs control cardiomyocyte function in development and disease. Collectively, this study mechanistically links cell signaling pathways as upstream regulators of HOPX transcription to control gene programs underpinning cardiomyocyte identity and function.PMID:38091997 | DOI:10.1016/j.devcel.2023.11.012

Source: Developmental Cell - December 13, 2023 Category: Cytology Authors: Clayton E Friedman Seth W Cheetham Sumedha Negi Richard J Mills Masahito Ogawa Meredith A Redd Han Sheng Chiu Sophie Shen Yuliangzi Sun Dalia Mizikovsky Romaric Bouveret Xiaoli Chen Holly K Voges Scott Paterson Jessica E De Angelis Stacey B Andersen Yuanz Source Type: research