The TCF7L2-PGC1α Axis Connects Mitochondrial Biogenesis And Metabolic Shift With Stem Cell Commitment To Hepatic Differentiation
(2017) Stem Cells : the international journal of cell differentiation and proliferation — Vol. August (2017)
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Sokal, Etienne 
- 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 TCF7L2 (transcription factor 7 like 2, a downstream effector of the Wnt/β-catenin pathway, repressed during differentiation) and PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1 alpha, 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. This article is protected by copyright. All rights reserved.
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Wanet, A., Caruso, M., Domelevo Entfellner, J.-B., Najar, M., Fattaccioli, A., Demazy, C., Evraerts, J., El Kehdy, H., Pourcher, G., Sokal, E., Arnould, T., Tiffin, N., Najimi, M., & Renard, P. (2017). The TCF7L2-PGC1α Axis Connects Mitochondrial Biogenesis And Metabolic Shift With Stem Cell Commitment To Hepatic Differentiation. Stem Cells : the international journal of cell differentiation and proliferation, August. https://doi.org/10.1002/stem.2688 (Original work published 2017)