Mitochondrial remodeling in hepatic differentiation and dedifferentiation

Anaïs Wanet, Noémie Remacle, Mehdi Najar, Etienne Sokal, Thierry Arnould, Mustapha Najimi, Patricia Renard

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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.

Original languageEnglish
Pages (from-to)174-185
Number of pages12
JournalThe international journal of Biochemistry & Cell biology
Volume54C
Early online date30 Jul 2014
DOIs
Publication statusPublished - 2014

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Organelle Biogenesis
Stem cells
Oxidative Phosphorylation
Liver
Induced Pluripotent Stem Cells
Mesenchymal Stromal Cells
Stem Cells
Bone Marrow
Adult Stem Cells
Mitochondrial Proteins
Glycolysis
Embryonic Stem Cells
Cell- and Tissue-Based Therapy
Bone
Mitochondrial DNA
Cell Differentiation
Hepatocytes
Mitochondria
Safety
Metabolism

Keywords

  • Oxidative phosphorylation
  • Hepatocytes
  • Mesenchymal stromal cells
  • Mitochondrial turnover
  • Cell (de)differentiation

Cite this

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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.",
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Mitochondrial remodeling in hepatic differentiation and dedifferentiation. / Wanet, Anaïs; Remacle, Noémie; Najar, Mehdi; Sokal, Etienne; Arnould, Thierry; Najimi, Mustapha; Renard, Patricia.

In: The international journal of Biochemistry & Cell biology, Vol. 54C, 2014, p. 174-185.

Research output: Contribution to journalArticle

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T1 - Mitochondrial remodeling in hepatic differentiation and dedifferentiation

AU - Wanet, Anaïs

AU - Remacle, Noémie

AU - Najar, Mehdi

AU - Sokal, Etienne

AU - Arnould, Thierry

AU - Najimi, Mustapha

AU - Renard, Patricia

N1 - Copyright © 2014 Elsevier Ltd. All rights reserved.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Oxidative phosphorylation

KW - Hepatocytes

KW - Mesenchymal stromal cells

KW - Mitochondrial turnover

KW - Cell (de)differentiation

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JF - The international journal of Biochemistry & Cell biology

SN - 1357-2725

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