Lipid availability determines fate of skeletal progenitor cells via SOX9

Nick van Gastel; Steve Stegen; Guy Eelen; Sandra Schoors; Aurélie Carlier; Veerle W Daniëls; Ninib Baryawno; Dariusz Przybylski; Maarten Depypere; Pieter-Jan Stiers; Dennis Lambrechts; Riet Van Looveren; Sophie Torrekens; Azeem Sharda; Patrizia Agostinis; Diether Lambrechts; Frederik Maes; Johan V Swinnen; Liesbet Geris; Hans Van Oosterwyck; Bernard Thienpont; Peter Carmeliet; David T Scadden; Geert Carmeliet

doi:10.1038/s41586-020-2050-1

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Lipid availability determines fate of skeletal progenitor cells via SOX9

Journal article

Open access

Peer reviewed

Lipid availability determines fate of skeletal progenitor cells via SOX9

Nick van Gastel, Steve Stegen, Guy Eelen, Sandra Schoors, Aurélie Carlier, Veerle W Daniëls, Ninib Baryawno, Dariusz Przybylski, Maarten Depypere, Pieter-Jan Stiers, …

Nature (London), Vol.579(7797), pp.111-117

03/2020

DOI: https://doi.org/10.1038/s41586-020-2050-1

PMID: 32103177

Abstract

SOX9 Transcription Factor - metabolism

Chondrocytes - cytology

Oxidation-Reduction

Mice, Inbred C57BL

Bone and Bones - blood supply

Cellular Microenvironment

Male

Stem Cells - cytology

Stem Cells - metabolism

Animals

Forkhead Transcription Factors - metabolism

Female

Food Deprivation

Mice

Chondrogenesis

Fatty Acids - metabolism

SOX9 Transcription Factor - genetics

Chondrocytes - metabolism

Osteogenesis

Bone and Bones - cytology

Signal Transduction

Lipid Metabolism

Wound Healing

The avascular nature of cartilage makes it a unique tissue, 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.

UN Sustainable Development Goals (SDGs)

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Title: Lipid availability determines fate of skeletal progenitor cells via SOX9
Creators: Nick van Gastel - Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA
Steve Stegen - Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium
Guy Eelen - Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium
Sandra Schoors - Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium
Aurélie Carlier - MERLN Institute of Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands
Veerle W Daniëls - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
Ninib Baryawno - Childhood Cancer Research Unit, Department of Children's and Women's Health, Karolinska Institutet, Stockholm, Sweden
Dariusz Przybylski - Howard Hughes Medical Institute and Department of Biology, Brandeis University, Waltham, MA, USA
Maarten Depypere - Department of Electrical Engineering, ESAT/PSI, Medical Image Computing, KU Leuven, Leuven, Belgium
Pieter-Jan Stiers - Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium
Dennis Lambrechts - Tissue Engineering Laboratory, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven, Belgium
Riet Van Looveren - Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
Sophie Torrekens - Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
Azeem Sharda - Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA
Patrizia Agostinis - Laboratory of Cell Death Research and Therapy, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
Diether Lambrechts - Laboratory of Translational Genetics, Center for Cancer Biology, VIB, Leuven, Belgium
Frederik Maes - Department of Electrical Engineering, ESAT/PSI, Medical Image Computing, KU Leuven, Leuven, Belgium
Johan V Swinnen - Laboratory of Lipid Metabolism and Cancer, Department of Oncology, KU Leuven, Leuven, Belgium
Liesbet Geris - Biomechanics Research Unit, GIGA In Silico Medicine, University of Liège, Liège, Belgium
Hans Van Oosterwyck - Biomechanics Section, Department of Mechanical Engineering, KU Leuven, Leuven, Belgium
Bernard Thienpont - Laboratory of Translational Genetics, Center for Cancer Biology, VIB, Leuven, Belgium
Peter Carmeliet - Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium
David T Scadden - Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA
Geert Carmeliet - Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium. geert.carmeliet@kuleuven.be
Publication Details: Nature (London), Vol.579(7797), pp.111-117
Grant note: 279100 / European Research Council 308223 / European Research Council
Identifiers: 9924012911801921
Academic Unit: Department of Biology
Language: English
Resource Type: Journal article

Lipid availability determines fate of skeletal progenitor cells via SOX9

Abstract

UN Sustainable Development Goals (SDGs)

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