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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Murine Mesenchymal Stem Cell Commitment to Differentiation Is Regulated by Mitochondrial Dynamics

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Author(s):
Forni, Maria Fernanda [1] ; Peloggia, Julia [1] ; Trudeau, Kyle [2] ; Shirihai, Orian [2] ; Kowaltowski, Alicia J. [1]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-01498 Sao Paulo - Brazil
[2] Boston Univ, Sch Med, Evans Biomed Res Ctr, Dept Med, Obes & Nutr Sect, Boston, MA 02215 - USA
Total Affiliations: 2
Document type: Journal article
Source: Stem Cells; v. 34, n. 3, p. 743-755, MAR 2016.
Web of Science Citations: 40
Abstract

Mouse skin mesenchymal stem cells (msMSCs) are dermis CD105(+)CD90(+)CD73(+)CD29(+)CD34(-) mesodermal precursors which, after in vitro induction, undergo chondro, adipo, and osteogenesis. Extensive metabolic reconfiguration has been found to occur during differentiation, and the bioenergetic status of a cell is known to be dependent on the quality and abundance of the mitochondrial population, which may be regulated by fusion and fission. However, little is known regarding the impact of mitochondrial dynamics on the differentiation process. We addressed this knowledge gap by isolating MSCs from Swiss female mice, inducing these cells to differentiate into osteo, chondro, and adipocytes and measuring changes in mass, morphology, dynamics, and bioenergetics. Mitochondrial biogenesis was increased in adipogenesis, as evaluated through confocal microscopy, citrate synthase activity, and mtDNA content. The early steps of adipo and osteogenesis involved mitochondrial elongation, as well as increased expression of mitochondrial fusion proteins Mfn1 and 2. Chondrogenesis involved a fragmented mitochondrial phenotype, increased expression of fission proteins Drp1, Fis1, and 2, and enhanced mitophagy. These events were accompanied by profound bioenergetic alterations during the commitment period. Moreover, knockdown of Mfn2 in adipo and osteogenesis and the overexpression of a dominant negative form of Drp1 during chondrogenesis resulted in a loss of differentiation ability. Overall, we find that mitochondrial morphology and its regulating processes of fission/fusion are modulated early on during commitment, leading to alterations in the bioenergetic profile that are important for differentiation. We thus propose a central role for mitochondrial dynamics in the maintenance/commitment of mesenchymal stem cells. (AU)

FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 14/17270-3 - Impact of mitochondrial dysfunction on skin aging
Grantee:Julia Peloggia de Castro
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 13/04871-6 - Effects of caloric restriction on mitochondrial morphology, dynamics, bioenergetics and redox state
Grantee:Maria Fernanda Pereira de Araújo Demonte Forni
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 10/51906-1 - Mitochondrial bioenergetics, ion transport, redox state and DNA metabolism
Grantee:Alicia Juliana Kowaltowski
Support type: Research Projects - Thematic Grants