ArticleAntioxidants & redox signaling2016
Heme Oxygenase-1/Carbon Monoxide System and Embryonic Stem Cell Differentiation and Maturation into Cardiomyocytes.
Article in Antioxidants & redox signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Heme oxygenase/carbon monoxide system and cardiac conduction system.Medical gas research · 2026Review
- Review
- Gasotransmitters and noble gases in cardioprotection: unraveling molecular pathways for future therapeutic strategies.Basic research in cardiology · 2024Review
- Nuclear respiratory factor-1 negatively regulates TGF-β1 and attenuates pulmonary fibrosis.iScience · 2022Article
- Anticancer and Antibiotic Rhenium Tri- and Dicarbonyl Complexes: Current Research and Future Perspectives.Molecules (Basel, Switzerland) · 2022Review
- Downregulation of Vascular Hemeoxygenase-1 Leads to Vasculopathy in Systemic Sclerosis.Frontiers in physiology · 2022Article
- Article
- Carbon monoxide and a change of heart.Redox biology · 2021Review
- Efficient Direct Nitrosylation of α-Diimine Rhenium Tricarbonyl Complexes to Structurally Nearly Identical Higher Charge Congeners Activable towards Photo-CO Release.Molecules (Basel, Switzerland) · 2021Article
- An Analysis of the Multifaceted Roles of Heme in the Pathogenesis of Cancer and Related Diseases.Cancers · 2021Review
- Nature's marvels endowed in gaseous molecules I: Carbon monoxide and its physiological and therapeutic roles.Acta pharmaceutica Sinica. B · 2021Review
- Role of Heme-Oxygenase-1 in Biology of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells.Cells · 2021Article
- Aerobically stable and substitutionally labile α-diimine rhenium dicarbonyl complexes.RSC advances · 2021Article
- Regulation of Endothelial and Vascular Functions by Carbon MonoxideFrontiers in cardiovascular medicine · 2021Review
- Article
- CO-mediated cytoprotection is dependent on cell metabolism modulation.Redox biology · 2020Review
- Roles of Reactive Oxygen Species in Cardiac Differentiation, Reprogramming, and Regenerative Therapies.Oxidative medicine and cellular longevity · 2020Review
- The Role of Reactive Oxygen Species in In Vitro Cardiac Maturation.Trends in molecular medicine · 2019Review
- CO-Releasing Materials: An Emphasis on Therapeutic Implications, as Release and Subsequent Cytotoxicity Are the Part of Therapy.Materials (Basel, Switzerland) · 2019Review
- P2X7 Receptors Mediate CO-Induced Alterations in Gene Expression in Cultured Cortical Astrocytes-Transcriptomic Study.Molecular neurobiology · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
aimsThe differentiation of embryonic stem (ES) cells into energetically efficient cardiomyocytes contributes to functional cardiac repair and is envisioned to ameliorate progressive degenerative cardiac diseases. Advanced cell maturation strategies are therefore needed to create abundant mature cardiomyocytes. In this study, we tested whether the redox-sensitive heme oxygenase-1/carbon monoxide (HO-1/CO) system, operating through mitochondrial biogenesis, acts as a mechanism for ES cell differentiation and cardiomyocyte maturation.
resultsManipulation of HO-1/CO to enhance mitochondrial biogenesis demonstrates a direct pathway to ES cell differentiation and maturation into beating cardiomyocytes that express adult structural markers. Targeted HO-1/CO interventions up- and downregulate specific cardiogenic transcription factors, transcription factor Gata4, homeobox protein Nkx-2.5, heart- and neural crest derivatives-expressed protein 1, and MEF2C. HO-1/CO overexpression increases cardiac gene expression for myosin regulatory light chain 2, atrial isoform, MLC2v, ANP, MHC-β, and sarcomere α-actinin and the major mitochondrial fusion regulators, mitofusin 2 and MICOS complex subunit Mic60. This promotes structural mitochondrial network expansion and maturation, thereby supporting energy provision for beating embryoid bodies. These effects are prevented by silencing HO-1 and by mitochondrial reactive oxygen species scavenging, while disruption of mitochondrial biogenesis and mitochondrial DNA depletion by loss of mitochondrial transcription factor A compromise infrastructure. This leads to failure of cardiomyocyte differentiation and maturation and contractile dysfunction. INNOVATION: The capacity to augment cardiomyogenesis via a defined mitochondrial pathway has unique therapeutic potential for targeting ES cell maturation in cardiac disease.
conclusionOur findings establish the HO-1/CO system and redox regulation of mitochondrial biogenesis as essential factors in ES cell differentiation as well as in the subsequent maturation of these cells into functional cardiac cells.
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Registered trials
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