Astro, VeronicaRamirez Calderon, GustavoPennucci, RobertaCaroli, JonatanSaera Vila, AlfonsoCardona Londoño, KellyForastieri, ChiaraFiacco, ElisabettaMaksoud, FatimaAlowaysi, MaryamSogne, ElisaFalqui, AndreaGonzález, FedericoMontserrat, NuriaBattaglioli, ElenaMattevi, AndreaAdamo, Antonio2022-09-062022-09-062022-07-152589-0042https://hdl.handle.net/2445/188730The histone demethylase KDM1A is a multi- faceted regulator of vital developmental processes, including mesodermal and cardiac tube formation during gastrulation. However, it is unknown whether the fine-tuning of KDM1A splicing isoforms, already shown to regulate neuronal maturation, is crucial for the specification and maintenance of cell identity during cardiogenesis. Here, we discovered a temporal modulation of ubKDM1A and KDM1A+2a during human and mice fetal cardiac development and evaluated their impact on the regulation of cardiac differentiation. We revealed a severely impaired cardiac differentiation in KDM1A(-/-) hESCs that can be rescued by re-expressing ubKDM1A or catalytically impaired ubKDM1A-K661A, but not by KDM1A+2a or KDM1A+2a-K661A. Conversely, KDM1A+2a(-/-) hESCs give rise to functional cardiac cells, displaying increased beating amplitude and frequency and enhanced expression of critical cardiogenic markers. Our findings prove the existence of a divergent scaffolding role of KDM1A splice variants, independent of their enzymatic activity, during hESC differentiation into cardiac cells.33 p.application/pdfengcc by-nc-nd (c) Astro, Veronica et al., 2022http://creativecommons.org/licenses/by-nc-nd/3.0/es/Cèl·lules mareRegulació genèticaCèl·lulesStem cellsGenetic regulationCellsinfo:eu-repo/semantics/article2022-09-05info:eu-repo/semantics/openAccess656403935856020