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bioRxiv · 10.64898/2026.11.09.761920

Adult-like thick-filament protein stoichiometry in immature human iPSC-derived cardiomyocytes

Ventura-Gomes, A.·Calheiros da Gama, M.·Furtado, M.·Carmo-Fonseca, M.
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Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) retain immature sarcomeric isoforms, raising questions about their ability to recapitulate the protein stoichiometry of adult human myocardium. We integrated two independent quantitative proteomic datasets of iPSC-CMs with published fetal and region-resolved adult human heart proteomes to compare sarcomeric protein abundance. Although iPSC-CMs clustered with fetal heart based on their global shared proteome and retained fetal troponin I expression, key thick-filament protein ratios closely matched those of adult myocardium. Myosin heavy-to-light chain ratios approached the expected 2:4 stoichiometry, while myosin-binding protein abundance relative to myosin heavy chains was comparable across iPSC-CMs and adult cardiac regions. These findings reveal that developmental immaturity in sarcomeric isoform expression does not entail altered thick-filament protein proportions. Preservation of adult-like myosin-binding protein stoichiometry supports the use of iPSC-CMs to investigate sarcomeric diseases associated with altered protein dosage, particularly MYBPC3-associated hypertrophic cardiomyopathy.

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Ventura-Gomes, A., Calheiros da Gama, M., Furtado, M., Carmo-Fonseca, M.. 2026-11-11. Adult-like thick-filament protein stoichiometry in immature human iPSC-derived cardiomyocytes. https://doi.org/10.64898/2026.11.09.761920

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