Alternative splicing dynamics during human cardiac development in vivo and in vitro

Gomes-Silva, Beatriz; Furtado, Marta; Ribeiro, Marta; Martins, Sandra; Carvalho, Teresa; Ventura-Gomes, André; Maatz, Henrike; Parakkat, Pragati; Crocini, Claudia; Gotthardt, Michael; Savisaar, Rosina; Carmo-Fonseca, Maria

Alternative splicing dynamics during human cardiac development in vivo and in vitro

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Item Type:	Article
Title:	Alternative splicing dynamics during human cardiac development in vivo and in vitro
Creators Name:	Gomes-Silva, Beatriz, Furtado, Marta, Ribeiro, Marta, Martins, Sandra, Carvalho, Teresa, Ventura-Gomes, André, Maatz, Henrike, Parakkat, Pragati, Crocini, Claudia, Gotthardt, Michael, Savisaar, Rosina and Carmo-Fonseca, Maria
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.
Keywords:	Alternative Splicing, Pluripotent Stem Cells, Cardiac Myocytes, Heart Development
Source:	Stem Cell Reports
ISSN:	2213-6711
Publisher:	Cell Press / Elsevier
Page Range:	102757
Date:	2 January 2026
Official Publication:	https://doi.org/10.1016/j.stemcr.2025.102757
PubMed:	View item in PubMed
Related to:	URL URL Type https://doi.org/10.6019/PXD070546 External Dataset https://github.com/bdgsilva/Cardiac-splicing-in-vivo-and-in-vitro Software

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