Authors
Beatriz Gomes-Silva, Marta Furtado, Marta Ribeiro, Sandra Martins, Teresa Carvalho, André Ventura-Gomes, Henrike Maatz, Pragati Parakkat, Claudia Crocini, Michael Gotthardt, Rosina Savisaar, Maria Carmo-Fonseca
Published in
Stem cell reports. Volume 21. Issue 1. Pages 102757. Jan 13, 2026. Epub Jan 02, 2026.
Abstract
Cardiomyocytes differentiated in vitro from human induced pluripotent stem cells (iPSC-CMs) are increasingly used in studies of disease mechanisms, drug development, toxicity testing, and regenerative medicine. Alternative splicing (AS) plays a pivotal role in cardiac development. However, the extent to which iPSC-CMs recapitulate native cardiac splicing patterns remains poorly understood. Here, we provide a comprehensive temporal map of AS regulation during human cardiac development. iPSC-derived cardiomyocytes globally recapitulate the transcriptome of prenatal cardiomyocytes, yet their splicing profiles remain heterogeneous, with certain events reflecting early embryonic patterns and others resembling those of later-stage fetal hearts. Moreover, we uncover altered splicing events in iPSC-CMs, including mis-splicing of splicing factors. In conclusion, we present a resource of AS dynamics throughout human cardiac development and a catalog of splicing markers to assess cardiomyocyte maturation in vitro. Our findings provide critical insights into the limitations of iPSC-CM models and their utility in cardiovascular research.
PMID:
41483812
Bibliographic data and abstract were imported from PubMed on 15 Sep 2026.
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