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

Research output: Contribution to journalArticle

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.

LanguageEnglish
Article number35(10)
Pages2184-2197
Number of pages14
JournalStem Cells
Volume35
Issue number10
Early online date27 Aug 2017
DOIs
StatePublished - 1 Oct 2017

Fingerprint

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

Keywords

  • Hepatic differentiation
  • Mitochondria
  • Oxidative phosphorylation
  • Stem cells
  • Wnt/β-catenin

Cite this

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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.",
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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.

In: Stem Cells, Vol. 35, No. 10, 35(10), 01.10.2017, p. 2184-2197.

Research output: Contribution to journalArticle

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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

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AU - Renard,Patricia

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KW - Oxidative phosphorylation

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