PMID- 28795454 OWN - NLM STAT- MEDLINE DCOM- 20180522 LR - 20180725 IS - 1549-4918 (Electronic) IS - 1066-5099 (Linking) VI - 35 IP - 10 DP - 2017 Oct TI - 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. PG - 2184-2197 LID - 10.1002/stem.2688 [doi] 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 remains poorly characterized. Here, we identified a transcriptional regulatory axis, composed of transcription factor 7-like 2 (TCF7L2) (a downstream effector of the Wnt/beta-catenin pathway, repressed during differentiation) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1alpha) (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-1alpha induction during differentiation is required for both mitochondrial biogenesis and commitment to the hepatocytic lineage, and TCF7L2 repression is sufficient to increase PGC-1alpha 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. Stem Cells 2017;35:2184-2197. CI - (c) 2017 AlphaMed Press. FAU - Wanet, Anais AU - Wanet A AUID- ORCID: 0000-0002-8058-2498 AD - Laboratory of Biochemistry and Cell Biology (URBC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium. FAU - Caruso, Marino AU - Caruso M AD - Laboratory of Biochemistry and Cell Biology (URBC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium. FAU - Domelevo Entfellner, Jean-Baka AU - Domelevo Entfellner JB AUID- ORCID: 0000-0002-8282-1325 AD - South African National Bioinformatics Institute (SANBI)/Medical Research Council of South Africa Bioinformatics Unit, University of the Western Cape, Bellville, South Africa. FAU - Najar, Mehdi AU - Najar M AD - Laboratory of Clinical Cell Therapy, Institut Jules Bordet, Universite Libre de Bruxelles (ULB), Brussels, Belgium. FAU - Fattaccioli, Antoine AU - Fattaccioli A AD - Laboratory of Biochemistry and Cell Biology (URBC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium. FAU - Demazy, Catherine AU - Demazy C AD - Laboratory of Biochemistry and Cell Biology (URBC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium. FAU - Evraerts, Jonathan AU - Evraerts J AD - Laboratory of Pediatric Hepatology and Cell Therapy, Universite Catholique de Louvain, Institut de Recherche Clinique et Experimentale (IREC), Brussels, Belgium. FAU - El-Kehdy, Hoda AU - El-Kehdy H AD - Laboratory of Pediatric Hepatology and Cell Therapy, Universite Catholique de Louvain, Institut de Recherche Clinique et Experimentale (IREC), Brussels, Belgium. FAU - Pourcher, Guillaume AU - Pourcher G AD - Department of Digestive Diseases, Institut Mutualiste Montsouris, Paris Descartes University, Paris, France. FAU - Sokal, Etienne AU - Sokal E AD - Laboratory of Pediatric Hepatology and Cell Therapy, Universite Catholique de Louvain, Institut de Recherche Clinique et Experimentale (IREC), Brussels, Belgium. FAU - Arnould, Thierry AU - Arnould T AD - Laboratory of Biochemistry and Cell Biology (URBC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium. FAU - Tiffin, Nicki AU - Tiffin N AD - South African National Bioinformatics Institute (SANBI)/Medical Research Council of South Africa Bioinformatics Unit, University of the Western Cape, Bellville, South Africa. FAU - Najimi, Mustapha AU - Najimi M AD - Laboratory of Pediatric Hepatology and Cell Therapy, Universite Catholique de Louvain, Institut de Recherche Clinique et Experimentale (IREC), Brussels, Belgium. FAU - Renard, Patricia AU - Renard P AUID- ORCID: 0000-0003-4144-3353 AD - Laboratory of Biochemistry and Cell Biology (URBC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170827 PL - England TA - Stem Cells JT - Stem cells (Dayton, Ohio) JID - 9304532 RN - 0 (CTNNB1 protein, human) RN - 0 (PPARGC1A protein, human) RN - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) RN - 0 (TCF7L2 protein, human) RN - 0 (Transcription Factor 7-Like 2 Protein) RN - 0 (beta Catenin) SB - IM MH - Cell Differentiation/physiology MH - Cells, Cultured MH - Hepatocytes/cytology/metabolism MH - Humans MH - Liver/*cytology/growth & development/*metabolism MH - Mitochondria, Liver/*metabolism MH - Organelle Biogenesis MH - Oxidative Phosphorylation MH - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/biosynthesis/genetics/*metabolism MH - Signal Transduction MH - Transcription Factor 7-Like 2 Protein/genetics/*metabolism MH - Transfection MH - beta Catenin/metabolism OTO - NOTNLM OT - Hepatic differentiation OT - Mitochondria OT - Oxidative phosphorylation OT - Stem cells OT - Wnt/beta-catenin EDAT- 2017/08/11 06:00 MHDA- 2018/05/23 06:00 CRDT- 2017/08/11 06:00 PHST- 2017/09/18 00:00 [received] PHST- 2017/07/12 00:00 [revised] PHST- 2017/07/15 00:00 [accepted] PHST- 2017/08/11 06:00 [pubmed] PHST- 2018/05/23 06:00 [medline] PHST- 2017/08/11 06:00 [entrez] AID - 10.1002/stem.2688 [doi] PST - ppublish SO - Stem Cells. 2017 Oct;35(10):2184-2197. doi: 10.1002/stem.2688. Epub 2017 Aug 27.