ArticleiScience2025
Serine synthesis pathway regulates cardiac differentiation from human pluripotent stem cells.
Article in iScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Molecular profiling of the single-cell proteome via gel electrophoresis and 3D single-molecule imaging.Nature communications · 2026Article
- Reduced Myocardial Serine Synthesis Impairs Functional, Metabolic, and Redox Adaptations to Cardiac Stress.bioRxiv : the preprint server for biology · 2026Article
- Elucidating Gene Functions in Congenital Heart Disease.Current treatment options in cardiovascular medicine · 2026Review
- Human induced pluripotent stem cell-derived cardiomyocytes for disease modeling and drug discovery.Frontiers in bioengineering and biotechnology · 2025Review
Corrections and comments
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Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human pluripotent stem cell-derived cardiomyocyte (hPSC-CM) differentiation can improve using chemical compounds which mimic early heart development. However, variations in hPSC-CM differentiation efficiency and its poor reproducibility have remained a challenge. Here, we report a unique metabolic method to promote hPSC-CM differentiation that involves marked suppression of the mitochondrial oxidative phosphorylation from the mesendoderm to the cardiac mesoderm, which is regulated by PHGDH, a rate-limiting enzyme in the serine synthesis pathway. Mechanistically, PHGDH inhibition impairs mitochondrial respiration by blocking the electron transport chain, resulting in elevated ROS levels and promoting the cardiomyocyte lineage specification by disrupting the cardiopharyngeal mesoderm lineage differentiation. Additionally, antioxidant supplementation can scavenge ROS and eliminate the effects of PHGDH inhibition. Collectively, our findings show that serine synthesis pathway can regulate cardiomyocyte lineage specification and have implications in providing a cellular source for transplantation and elucidating the potential mechanisms of heart development and pathogenesis of heart disease.
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Registered trials
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