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| Item Type: | Preprint |
|---|---|
| Title: | Alternative splicing dynamics during human cardiac development in vivo and in vitro |
| Creators Name: | Gomes-Silva, B., Furtado, M., Ribeiro, M., Martins, S., Carvalho, M.T., Ventura-Gomes, A., Maatz, H., Parakkat, P.N., Gotthardt, M., Savisaar, R. and Carmo-Fonseca, M. |
| 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), a crucial mechanism for regulating gene expression during development, plays a pivotal role in cardiac differentiation and maturation. 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. In addition to the major splicing changes occurring perinatally, we identify finely tuned prenatal splicing transitions. 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 heart development. 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: | bioRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2025.03.21.642423v2 |
| Date: | 27 October 2025 |
| Official Publication: | https://doi.org/10.1101/2025.03.21.642423 |
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