The Transcription Factor 7-Like 2-Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Axis Connects Mitochondrial Biogenesis and Metabolic Shift with Stem Cell Commitment to Hepatic Differentiation

Anaïs Wanet, Marino Caruso, Jean Baka Domelevo Entfellner, Mehdi Najar, Antoine Fattaccioli, Catherine Demazy, Jonathan Evraerts, Hoda El-Kehdy, Guillaume Pourcher, Etienne Sokal, Thierry Arnould, Nicki Tiffin, Mustapha Najimi, Patricia Renard

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

Increasing evidence supports that modifications in the mitochondrial content, oxidative phosphorylation (OXPHOS) activity, and cell metabolism influence the fate of stem cells. However, the regulators involved in the crosstalk between mitochondria and stem cell fate remain poorly characterized. Here, we identified a transcriptional regulatory axis, composed of transcription factor 7-like 2 (TCF7L2) (a downstream effector of the Wnt/β-catenin pathway, repressed during differentiation) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) (the master regulator of mitochondrial biogenesis, induced during differentiation), coupling the loss of pluripotency and early commitment to differentiation, to the initiation of mitochondrial biogenesis and metabolic shift toward OXPHOS. PGC-1α induction during differentiation is required for both mitochondrial biogenesis and commitment to the hepatocytic lineage, and TCF7L2 repression is sufficient to increase PGC-1α expression, mitochondrial biogenesis and OXPHOS activity. We further demonstrate that OXPHOS activity is required for the differentiation toward the hepatocytic lineage, thus providing evidence that bi-directional interactions control stem cell differentiation and mitochondrial abundance and activity.

langueAnglais
Numéro d'article35(10)
Pages2184-2197
Nombre de pages14
journalStem Cells
Volume35
Numéro10
Date de mise en ligne précoce27 août 2017
Les DOIs
étatPublié - 1 oct. 2017

Empreinte digitale

T Cell Transcription Factor 1
Oxidative Phosphorylation
Organelle Biogenesis
Stem Cells
Liver
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
beta Catenin
Cell Differentiation
Mitochondria

mots-clés

    Citer ceci

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    title = "The Transcription Factor 7-Like 2-Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Axis Connects Mitochondrial Biogenesis and Metabolic Shift with Stem Cell Commitment to Hepatic Differentiation",
    abstract = "Increasing evidence supports that modifications in the mitochondrial content, oxidative phosphorylation (OXPHOS) activity, and cell metabolism influence the fate of stem cells. However, the regulators involved in the crosstalk between mitochondria and stem cell fate remain poorly characterized. Here, we identified a transcriptional regulatory axis, composed of transcription factor 7-like 2 (TCF7L2) (a downstream effector of the Wnt/β-catenin pathway, repressed during differentiation) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) (the master regulator of mitochondrial biogenesis, induced during differentiation), coupling the loss of pluripotency and early commitment to differentiation, to the initiation of mitochondrial biogenesis and metabolic shift toward OXPHOS. PGC-1α induction during differentiation is required for both mitochondrial biogenesis and commitment to the hepatocytic lineage, and TCF7L2 repression is sufficient to increase PGC-1α expression, mitochondrial biogenesis and OXPHOS activity. We further demonstrate that OXPHOS activity is required for the differentiation toward the hepatocytic lineage, thus providing evidence that bi-directional interactions control stem cell differentiation and mitochondrial abundance and activity.",
    keywords = "Hepatic differentiation, Mitochondria, Oxidative phosphorylation, Stem cells, Wnt/β-catenin",
    author = "Ana\{"i}s Wanet and Marino Caruso and {Domelevo Entfellner}, {Jean Baka} and Mehdi Najar and Antoine Fattaccioli and Catherine Demazy and Jonathan Evraerts and Hoda El-Kehdy and Guillaume Pourcher and Etienne Sokal and Thierry Arnould and Nicki Tiffin and Mustapha Najimi and Patricia Renard",
    year = "2017",
    month = "10",
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    doi = "10.1002/stem.2688",
    language = "English",
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    The Transcription Factor 7-Like 2-Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Axis Connects Mitochondrial Biogenesis and Metabolic Shift with Stem Cell Commitment to Hepatic Differentiation. / Wanet, Anaïs; Caruso, Marino; Domelevo Entfellner, Jean Baka; Najar, Mehdi; Fattaccioli, Antoine; Demazy, Catherine; Evraerts, Jonathan; El-Kehdy, Hoda; Pourcher, Guillaume; Sokal, Etienne; Arnould, Thierry; Tiffin, Nicki; Najimi, Mustapha; Renard, Patricia.

    Dans: Stem Cells, Vol 35, Numéro 10, 35(10), 01.10.2017, p. 2184-2197.

    Résultats de recherche: Contribution à un journal/une revueArticle

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    T1 - The Transcription Factor 7-Like 2-Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Axis Connects Mitochondrial Biogenesis and Metabolic Shift with Stem Cell Commitment to Hepatic Differentiation

    AU - Wanet,Anaïs

    AU - Caruso,Marino

    AU - Domelevo Entfellner,Jean Baka

    AU - Najar,Mehdi

    AU - Fattaccioli,Antoine

    AU - Demazy,Catherine

    AU - Evraerts,Jonathan

    AU - El-Kehdy,Hoda

    AU - Pourcher,Guillaume

    AU - Sokal,Etienne

    AU - Arnould,Thierry

    AU - Tiffin,Nicki

    AU - Najimi,Mustapha

    AU - Renard,Patricia

    PY - 2017/10/1

    Y1 - 2017/10/1

    N2 - Increasing evidence supports that modifications in the mitochondrial content, oxidative phosphorylation (OXPHOS) activity, and cell metabolism influence the fate of stem cells. However, the regulators involved in the crosstalk between mitochondria and stem cell fate remain poorly characterized. Here, we identified a transcriptional regulatory axis, composed of transcription factor 7-like 2 (TCF7L2) (a downstream effector of the Wnt/β-catenin pathway, repressed during differentiation) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) (the master regulator of mitochondrial biogenesis, induced during differentiation), coupling the loss of pluripotency and early commitment to differentiation, to the initiation of mitochondrial biogenesis and metabolic shift toward OXPHOS. PGC-1α induction during differentiation is required for both mitochondrial biogenesis and commitment to the hepatocytic lineage, and TCF7L2 repression is sufficient to increase PGC-1α expression, mitochondrial biogenesis and OXPHOS activity. We further demonstrate that OXPHOS activity is required for the differentiation toward the hepatocytic lineage, thus providing evidence that bi-directional interactions control stem cell differentiation and mitochondrial abundance and activity.

    AB - Increasing evidence supports that modifications in the mitochondrial content, oxidative phosphorylation (OXPHOS) activity, and cell metabolism influence the fate of stem cells. However, the regulators involved in the crosstalk between mitochondria and stem cell fate remain poorly characterized. Here, we identified a transcriptional regulatory axis, composed of transcription factor 7-like 2 (TCF7L2) (a downstream effector of the Wnt/β-catenin pathway, repressed during differentiation) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) (the master regulator of mitochondrial biogenesis, induced during differentiation), coupling the loss of pluripotency and early commitment to differentiation, to the initiation of mitochondrial biogenesis and metabolic shift toward OXPHOS. PGC-1α induction during differentiation is required for both mitochondrial biogenesis and commitment to the hepatocytic lineage, and TCF7L2 repression is sufficient to increase PGC-1α expression, mitochondrial biogenesis and OXPHOS activity. We further demonstrate that OXPHOS activity is required for the differentiation toward the hepatocytic lineage, thus providing evidence that bi-directional interactions control stem cell differentiation and mitochondrial abundance and activity.

    KW - Hepatic differentiation

    KW - Mitochondria

    KW - Oxidative phosphorylation

    KW - Stem cells

    KW - Wnt/β-catenin

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    U2 - 10.1002/stem.2688

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    M3 - Article

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    JO - Stem Cells

    T2 - Stem Cells

    JF - Stem Cells

    SN - 1066-5099

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