ArticleCell stem cell2022
PPARdelta activation induces metabolic and contractile maturation of human pluripotent stem cell-derived cardiomyocytes.
Article in Cell stem cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 3 of them syntheses that pooled it.
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Who cites it
61 citing papers in PubMed, 3 syntheses or guidelines pooled it, 91 citations in OpenAlex.
- Engineering the maturation of stem cell-derived cardiomyocytes.Frontiers in bioengineering and biotechnology · 2023Pooled it
- Using human induced pluripotent stem cell-derived cardiomyocytes to understand the mechanisms driving cardiomyocyte maturation.Frontiers in cardiovascular medicine · 2022Pooled it
- Cannabidiol effects in stem cells: A systematic review.BioFactors (Oxford, England)Pooled it
- Spatially guided in vivo single-cell functional genomics of postnatal heart.Nature cardiovascular research · 2026Article
- Tubular ACSM3 controls fatty acid metabolism and safeguards against acute kidney injury in male mice.Nature communications · 2026Article
- Mechanical Loading Induces Distinct and Shared Responses in Endothelial and Muscle Cells and Reveals Exercise-Like Molecular Profiles.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Differences of PPARD Expression in the Liver of Cattle with Different Marbling Grades.Animals : an open access journal from MDPI · 2026Article
- Impact of maternal lipopolysaccharide and polyinosinic-polycytidylic acid-induced infections on offspring cardiac development: Mitochondrial dysfunction and metabolic alterations.Genes & diseases · 2026Article
- Models of the human heart for biomedical research: Opportunities and challenges.Physiological reports · 2026Review
- Advanced physiological maturation of human iPSC-derived cardiomyocytes using an algorithm-directed optimization of defined media components.Nature communications · 2026Article
- Single-Cell Multi-Omics Reveal Gene Regulatory Mechanisms Underlying Cardiac Embryonic Development.Genes · 2026Review
- NAMing the challenges and opportunities of new approach methodologies for studying cardiovascular metabolism.Cell metabolism · 2026Article
- Article
- Circulating Extracellular Vesicles in the Pathogenesis of Heart Failure in Patients With Chronic Kidney Disease.Circulation · 2026Article
- 3D Cardiac Constructs in Drug Discovery: Current Advances and Future Challenges.Research (Washington, D.C.) · 2026Review
- TCA cycle intermediates as an adjunct strategy for human iPSC-derived cardiomyocyte maturation.BBA advances · 2026Article
- Mitochondrial regulation of lactylation in sepsis-induced cardiomyopathy.Critical care (London, England) · 2025Review
- Substrate stiffness-dependent metabolic reprogramming of iPSC-derived cardiomyocytes on physiological PDMS polymers.Metabolic engineering communications · 2025Article
- A Micro-Engineered Heart Tissue Model of Desmin-related Cardiomyopathy Caused by Mutant αB Crystallin.bioRxiv : the preprint server for biology · 2025Article
- Neuroectoderm-derived iris muscle characterization at the single-cell resolution in native human iris and a pluripotent stem cell eye model.Nature communications · 2025Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 5 institutions in 2 countries.
Funding
Abstract
Pluripotent stem-cell-derived cardiomyocytes (PSC-CMs) provide an unprecedented opportunity to study human heart development and disease, but they are functionally and structurally immature. Here, we induce efficient human PSC-CM (hPSC-CM) maturation through metabolic-pathway modulations. Specifically, we find that peroxisome-proliferator-associated receptor (PPAR) signaling regulates glycolysis and fatty acid oxidation (FAO) in an isoform-specific manner. While PPARalpha (PPARa) is the most active isoform in hPSC-CMs, PPARdelta (PPARd) activation efficiently upregulates the gene regulatory networks underlying FAO, increases mitochondrial and peroxisome content, enhances mitochondrial cristae formation, and augments FAO flux. PPARd activation further increases binucleation, enhances myofibril organization, and improves contractility. Transient lactate exposure, which is frequently used for hPSC-CM purification, induces an independent cardiac maturation program but, when combined with PPARd activation, still enhances oxidative metabolism. In summary, we investigate multiple metabolic modifications in hPSC-CMs and identify a role for PPARd signaling in inducing the metabolic switch from glycolysis to FAO in hPSC-CMs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.