ArticleMolecular biology of the cell2003
A dual role of the GTPase Rac in cardiac differentiation of stem cells.
Article in Molecular biology of the cell, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 58 citations in OpenAlex.
- Roles of Reactive Oxygen Species in Cardiac Differentiation, Reprogramming, and Regenerative Therapies.Oxidative medicine and cellular longevity · 2020Review
- Cardiac Cell Senescence and Redox Signaling.Frontiers in cardiovascular medicine · 2017Review
- Redox signaling in cardiac renewal.Antioxidants & redox signaling · 2014Review
- Article
- Electrical stimulation promotes maturation of cardiomyocytes derived from human embryonic stem cells.Journal of cardiovascular translational research · 2013Article
- Nox2 and Nox4 influence neonatal c-kit(+) cardiac precursor cell status and differentiation.American journal of physiology. Heart and circulatory physiology · 2013Article
- NADPH oxidase 4 regulates cardiomyocyte differentiation via redox activation of c-Jun protein and the cis-regulation of GATA-4 gene transcription.The Journal of biological chemistry · 2013Article
- Energy metabolism plasticity enables stemness programs.Annals of the New York Academy of Sciences · 2012Review
- Mitochondria in control of cell fate.Circulation research · 2012Article
- Redox signaling in cardiac myocytes.Free radical biology & medicine · 2011Review
- Electrical stimulation of human embryonic stem cells: cardiac differentiation and the generation of reactive oxygen species.Experimental cell research · 2009Article
- Novel role of NADPH oxidase in angiogenesis and stem/progenitor cell function.Antioxidants & redox signaling · 2009Review
- Redox modifier genes and pathways in amyotrophic lateral sclerosis.Antioxidants & redox signaling · 2009Review
- Mechanical control of tissue morphogenesis.Circulation research · 2008Review
- SOD1 mutations disrupt redox-sensitive Rac regulation of NADPH oxidase in a familial ALS model.The Journal of clinical investigation · 2008Article
- Inositol-1,4,5-trisphosphate-mediated spontaneous activity in mouse embryonic stem cell-derived cardiomyocytes.The Journal of physiology · 2007Article
- The NADPH oxidase NOX4 drives cardiac differentiation: Role in regulating cardiac transcription factors and MAP kinase activation.Molecular biology of the cell · 2006Article
- Cardiac repair by embryonic stem-derived cells.Handbook of experimental pharmacology · 2006Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The function of the GTPase Rac1, a molecular switch transducing intracellular signals from growth factors, in differentiation of a specific cell type during early embryogenesis has not been investigated. To address the question, we used embryonic stem (ES) cells differentiated into cardiomyocytes, a model that faithfully recapitulates early stages of cardiogenesis. Overexpression in ES cells of a constitutively active Rac (RacV12) but not of an active mutant (RacL61D38), which does not activate the NADPH oxydase generating ROS, prevented MEF2C expression and severely compromised cardiac cell differentiation. This resulted in poor expression of ventricular myosin light chain 2 (MLC2v) and its lack of insertion into sarcomeres. Thus ES-derived cardiomyocytes featured impaired myofibrillogenesis and contractility. Overexpression of MEF2C or addition of catalase in the culture medium rescued the phenotype of racV12 cells. In contrast, RacV12 specifically expressed in ES-derived ventricular cells improved the propensity of cardioblasts to differentiate into beating cardiomyocytes. This was attributed to both a facilitation of myofibrillogenesis and a prolongation in their proliferation. The dominant negative mutant RacN17 early or lately expressed in ES-derived cells prevented myofibrillogenesis and in turn beating of cardiomyocytes. We thus suggest a stage-dependent function of the GTPase during early embryogenesis.
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Registered trials
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