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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: Gomes-Silva, Beatriz, Furtado, Marta ORCID logoORCID: https://orcid.org/0000-0003-3714-9653, Ribeiro, Marta, Martins, Sandra, Carvalho, Teresa, Ventura-Gomes, André, Maatz, Henrike ORCID logoORCID: https://orcid.org/0000-0002-9232-6272, Parakkat, Pragati ORCID logoORCID: https://orcid.org/0000-0003-2691-791X, Crocini, Claudia, Gotthardt, Michael ORCID logoORCID: https://orcid.org/0000-0003-1788-3172, Savisaar, Rosina and Carmo-Fonseca, Maria ORCID logoORCID: https://orcid.org/0000-0002-3402-7143
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:Cardiac Myocytes, Pluripotent Stem Cells, Cell Differentiation, Developmental Gene Expression Regulation, Heart, Induced Pluripotent Stem Cells, Organogenesis, Transcriptome
Source:Stem Cell Reports
ISSN:2213-6711
Publisher:Cell Press / Elsevier
Volume:21
Number:1
Page Range:102757
Date:13 January 2026
Official Publication:https://doi.org/10.1016/j.stemcr.2025.102757
PubMed:View item in PubMed
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