title: Mitochondrial respiration regulates adipogenic differentiation of human mesenchymal stem cells.
abstract: Human mesenchymal stem cells (MSCs) are adult multipotent stem cells which can be isolated from bone marrow, adipose tissue as well as other tissues and have the capacity to differentiate into a variety of mesenchymal cell types such as adipocytes, osteoblasts and chondrocytes. Differentiation of stem cells into mature cell types is guided by growth factors and hormones, but recent studies suggest that metabolic shifts occur during differentiation and can modulate the differentiation process. We therefore investigated mitochondrial biogenesis, mitochondrial respiration and the mitochondrial membrane potential during adipogenic differentiation of human MSCs. In addition, we inhibited mitochondrial function to assess its effects on adipogenic differentiation. Our data show that mitochondrial biogenesis and oxygen consumption increase markedly during adipogenic differentiation, and that reducing mitochondrial respiration by hypoxia or by inhibition of the mitochondrial electron transport chain significantly suppresses adipogenic differentiation. Furthermore, we used a novel approach to suppress mitochondrial activity using a specific siRNA-based knockdown of the mitochondrial transcription factor A (TFAM), which also resulted in an inhibition of adipogenic differentiation. Taken together, our data demonstrates that increased mitochondrial activity is a prerequisite for MSC differentiation into adipocytes. These findings suggest that metabolic modulation of adult stem cells can maintain stem cell pluripotency or direct adult stem cell differentiation.
authors.affiliation: Section of Cardiology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Glenn
authors.initials: G
authors.lastname: Marsboom
authors.forename: Peter T
authors.initials: PT
authors.lastname: Toth
authors.forename: Jalees
authors.initials: J
authors.lastname: Rehman
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis; D000328:Adult; D002454:Cell Differentiation; D015687:Cell Hypoxia; D019069:Cell Respiration; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D053078:Membrane Potential, Mitochondrial; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D014157:Transcription Factors; C422562:mitochondrial transcription factor A