Article (Scientific journals)
Lipid availability determines fate of skeletal progenitor cells via SOX9
van Gastel, N.; Stegen, S.; Eelen, G. et al.
2020In Nature, 579 (7797), p. 111-117
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Abstract :
[en] The avascular nature of cartilage makes it a unique tissue1–4, but whether and how the absence of nutrient supply regulates chondrogenesis remain unknown. Here we show that obstruction of vascular invasion during bone healing favours chondrogenic over osteogenic differentiation of skeletal progenitor cells. Unexpectedly, this process is driven by a decreased availability of extracellular lipids. When lipids are scarce, skeletal progenitors activate forkhead box O (FOXO) transcription factors, which bind to the Sox9 promoter and increase its expression. Besides initiating chondrogenesis, SOX9 acts as a regulator of cellular metabolism by suppressing oxidation of fatty acids, and thus adapts the cells to an avascular life. Our results define lipid scarcity as an important determinant of chondrogenic commitment, reveal a role for FOXO transcription factors during lipid starvation, and identify SOX9 as a critical metabolic mediator. These data highlight the importance of the nutritional microenvironment in the specification of skeletal cell fate. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
Disciplines :
Engineering, computing & technology: Multidisciplinary, general & others
Author, co-author :
van Gastel, N.;  Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium, Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, United States, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, United States, Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, United States
Stegen, S.;  Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium, Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium
Eelen, G.;  Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, Leuven, Belgium, Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium
Schoors, S.;  Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, Leuven, Belgium, Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium
Carlier, Aurélie ;  Université de Liège - ULiège
Daniëls, V. W.;  Laboratory of Lipid Metabolism and Cancer, Department of Oncology, KU Leuven, Leuven, Belgium, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
Baryawno, N.;  Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, United States, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, United States, Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, United States, Childhood Cancer Research Unit, Department of Children’s and Women’s Health, Karolinska Institutet, Stockholm, Sweden
Przybylski, D.;  Howard Hughes Medical Institute and Department of Biology, Brandeis University, Waltham, MA, United States
Depypere, M.;  Medical Imaging Research Center, KU Leuven, Leuven, Belgium, Department of Electrical Engineering, ESAT/PSI, Medical Image Computing, KU Leuven, Leuven, Belgium
Stiers, P.-J.;  Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium, Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium
Lambrechts, D.;  Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium, Centre for Surface Chemistry and Catalysis, Department of Microbial and Molecular Systems, KU Leuven, Leuven, Belgium, Tissue Engineering Laboratory, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven, Belgium
Van Looveren, R.;  Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
Torrekens, S.;  Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
Sharda, A.;  Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, United States, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, United States, Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, United States
Agostinis, P.;  Laboratory of Cell Death Research and Therapy, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
Lambrechts, D.;  Laboratory of Translational Genetics and Laboratory for Functional Epigenetics, Department of Human Genetics, KU Leuven, Leuven, Belgium, Laboratory of Translational Genetics, Center for Cancer Biology, VIB, Leuven, Belgium
Maes, F.;  Medical Imaging Research Center, KU Leuven, Leuven, Belgium, Department of Electrical Engineering, ESAT/PSI, Medical Image Computing, KU Leuven, Leuven, Belgium
Swinnen, J. V.;  Laboratory of Lipid Metabolism and Cancer, Department of Oncology, KU Leuven, Leuven, Belgium
Geris, Liesbet  ;  Université de Liège - ULiège > Département d'aérospatiale et mécanique > Génie biomécanique
Van Oosterwyck, H.;  Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium, Biomechanics Section, Department of Mechanical Engineering, KU Leuven, Leuven, Belgium
Thienpont, B.;  Laboratory of Translational Genetics and Laboratory for Functional Epigenetics, Department of Human Genetics, KU Leuven, Leuven, Belgium, Laboratory of Translational Genetics, Center for Cancer Biology, VIB, Leuven, Belgium
Carmeliet, P.;  Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, Leuven, Belgium, Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium
Scadden, D. T.;  Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, United States, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, United States, Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, United States
Carmeliet, G.;  Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium, Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium
More authors (14 more) Less
Language :
English
Title :
Lipid availability determines fate of skeletal progenitor cells via SOX9
Publication date :
2020
Journal title :
Nature
ISSN :
0028-0836
eISSN :
1476-4687
Publisher :
Nature Publishing Group, London, United Kingdom
Volume :
579
Issue :
7797
Pages :
111-117
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
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