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Retinoic acid activation of the ERK pathway is required for embryonic stem cell commitment into the adipocyte lineage
Open accessAbstract
Mouse embryonic stem (ES) cells are pluripotent cells that differentiate into multiple cell lineages. The commitment of ES cells into the adipocyte lineage is dependent on an early 3-day treatment with all-trans retinoic acid (RA). To characterize the molecular mechanisms underlying this process, we examined the contribution of the extracellular-signal-regulated kinase (ERK) pathway. Treatment of ES cell-derived embryoid bodies with RA resulted in a prolonged activation of the ERK pathway, but not the c-Jun N-terminal kinase, p38 mitogen-activated protein kinase or phosphoinositide 3-kinase pathways. To investigate the role of ERK activation, co-treatment of RA with PD98059, a specific inhibitor of the ERK signalling pathway, prevented both adipocyte formation and expression of the adipogenic markers, adipocyte lipid-binding protein and peroxisome-proliferator-activated receptor γ. Furthermore, we show that ERK activation is required only during RA treatment. PD98059 does not interfere with the commitment of ES cells into other lineages, such as neurogenesis, myogenesis and cardiomyogenesis. As opposed to the controversial role of the ERK pathway in terminal differentiation, our results clearly demonstrate that this pathway is specifically required at an early stage of adipogenesis, corresponding to the RA-dependent commitment of ES cells.
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“However, in neuronal cells, Sertoli cells, and embryonic stem cells, RA instead activates the p42/p44 extracellular signal-regulated kinases (Erk) or classical MAPKs ( 116-122 ).”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [118]
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Metadata
- Authors
- BOST, F., CARON, L., MARCHETTI, I., DANI, C., MARCHAND-BRUSTEL, Y. L., & BINÉTRUY, B.
- Affiliations
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- INSERM E9911 and IFR50, Faculté de Médecine, Université de Nice Sophia Antipolis, Avenue de Valombrose, Nice 06107, France
- Corresponding author
- CARON, Leslie
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2002-01-25
- Volume
- 361
- Issue
- 3
- Pages
- 621-627
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1222345
- OpenAlex
- W1963496112
- Cited by
- 184
- References
- 47
- Citations by year
- 2024: 2 · 2023: 3 · 2022: 2 · 2021: 7 · 2020: 7 · 2019: 7 · 2018: 2 · 2017: 11 · 2016: 7 · 2015: 7 · 2014: 7 · 2013: 15 · 2012: 13
- FWCI
- 3.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centre National de la Recherche Scientifique
- Servier
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- retinoic acid, ERK signaling, embryonic stem cells, adipogenesis, lineage commitment, PD98059, embryoid bodies, PPARγ, adipocyte lipid-binding protein, MAPK signaling, pluripotency
- MeSH terms
- Animals, Butadienes, Embryo, Mammalian, Enzyme Activation, Enzyme Inhibitors, Flavonoids, Imidazoles, Myocardium, Neurons, Nitriles, Protein Binding, Pyridines, RNA, Stem Cells, Time Factors, Transcription Factors, Tretinoin, Signal Transduction, Adipocytes, Receptors, Cytoplasmic and Nuclear, Cell Lineage, Phosphatidylinositol 3-Kinases, Mitogen-Activated Protein Kinases, JNK Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, Mice
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