Cited by 184Pluripotent Stem Cells ResearchPeroxisome Proliferator-Activated ReceptorsAdipose Tissue and Metabolism

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Retinoic acid activation of the ERK pathway is required for embryonic stem cell commitment into the adipocyte lineage

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BOST, Frédéric, CARON, Leslie, MARCHETTI, Irène, DANI, Christian, MARCHAND-BRUSTEL, Yannick LE, BINÉTRUY, Bernard·2002·Biochemical Journal

DOI 10.1042/bj3610621PMC PMC1222345

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Abstract

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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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
ORCID: BOST, Frédéric
CARON, Leslie
MARCHETTI, Irène
DANI, Christian
BINÉTRUY, Bernard
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
DOI: 10.1042/bj3610621
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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Retinoic acid activation of the ERK pathway is required for embryonic stem cell commitment into the adipocyte lineage

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