CSDC2, an RBP essential to cardiomyocyte commitment during cardiac differentiation in hiPSC

Abstract Cardiovascular diseases are the leading cause of death worldwide, accounting for approximately 30% of total mortality. Changes in post-transcriptional regulation have been correlated with the development of cardiopathies. RNA-binding proteins (RBP) are proteins capable of interacting with mRNAs, regulating their stability, localization, and translation. Here, we described CSDC2 as an RBP expressed at the final stages of cardiac differentiation using hPSCs as a model. We showed that the loss of CSDC2 impairs cardiomyocyte differentiation, while the recovery of its expression rescues the differentiation potential of these cells. We characterized the translatome of CSDC2 knockout cells during cardiac differentiation by polysome profiling. In cardiac mesoderm cells, CSDC2 interacts with ribosomal proteins. Furthermore, CSDC2 appears to be able to associate with mRNAs encoding regulators of cardiac progenitor commitment. Altogether, in this study, we describe a new role of CSDC2 in cardiomyocyte commitment using cardiac differentiation of hiPSCs.