title: Mitochondrial remodeling in hepatic differentiation and dedifferentiation.
abstract: Mitochondrial biogenesis and metabolism have recently emerged as important actors of stemness and differentiation. On the one hand, the differentiation of stem cells is associated with an induction of mitochondrial biogenesis and a shift from glycolysis toward oxidative phosphorylations (OXPHOS). In addition, interfering with mitochondrial biogenesis or function impacts stem cell differentiation. On the other hand, some inverse changes in mitochondrial abundance and function are observed during the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). Yet although great promises in cell therapy might generate better knowledge of the mechanisms regulating the stemness and differentiation of somatic stem cells (SSCs)-which are preferred over embryonic stem cells (ESCs) and iPSCs because of ethical and safety considerations-little interest was given to the study of their mitochondria. This study provides a detailed characterization of the mitochondrial biogenesis occurring during the hepatogenic differentiation of bone marrow-mesenchymal stem cells (BM-MSCs). During the hepatogenic differentiation of BM-MSCs, an increased abundance of mitochondrial DNA (mtDNA) is observed, as well as an increased expression of several mitochondrial proteins and biogenesis regulators, concomitant with increased OXPHOS activity, capacity, and efficiency. In addition, opposite changes in mitochondrial morphology and in the abundance of several OXPHOS subunits were found during the spontaneous dedifferentiation of primary hepatocytes. These data support reverse mitochondrial changes in a different context from genetically-engineered reprogramming. They argue in favor of a mitochondrial involvement in hepatic differentiation and dedifferentiation.
authors.affiliation: Laboratory of Biochemistry and Cell Biology (URBC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur (UNamur), 61 rue de Bruxelles, 5000 Namur, Belgium. Electronic address: anais.wanet@unamur.be.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Wanet
authors.affiliation: Laboratory of Biochemistry and Cell Biology (URBC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur (UNamur), 61 rue de Bruxelles, 5000 Namur, Belgium. Electronic address: noemie.remacle@hotmail.fr.
authors.forename: Noémie
authors.initials: N
authors.lastname: Remacle
authors.affiliation: Laboratory of Clinical Cell Therapy, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Brussels, Belgium. Electronic address: Mehdi.Najar@ulb.ac.be.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Najar
authors.affiliation: Université Catholique de Louvain, Institut de Recherche Clinique et Expérimentale (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, Brussels, Belgium. Electronic address: etienne.sokal@uclouvain.be.
authors.forename: Etienne
authors.initials: E
authors.lastname: Sokal
authors.affiliation: Laboratory of Biochemistry and Cell Biology (URBC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur (UNamur), 61 rue de Bruxelles, 5000 Namur, Belgium. Electronic address: thierry.arnould@unamur.be.
authors.forename: Thierry
authors.initials: T
authors.lastname: Arnould
authors.affiliation: Université Catholique de Louvain, Institut de Recherche Clinique et Expérimentale (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, Brussels, Belgium. Electronic address: mustapha.najimi@uclouvain.be.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Najimi
authors.affiliation: Laboratory of Biochemistry and Cell Biology (URBC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur (UNamur), 61 rue de Bruxelles, 5000 Namur, Belgium. Electronic address: patsy.renard@unamur.be.
authors.forename: Patricia
authors.initials: P
authors.lastname: Renard
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics*; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D063269:Mitochondrial Turnover / Q000502:physiology*; D010085:Oxidative Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D012333:RNA, Messenger
keywords: Cell (de)differentiation; Hepatocytes; Mesenchymal stromal cells; Mitochondrial turnover; Oxidative phosphorylation