Lipid Availability Determines Skeletal Progenitor Cell Fate via SOX9
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Stegen, Steve
Eelen, Guy
Schoors, Sandra
Carlier, Aurélie
Daniëls, Veerle W.
Baryawno, Ninib
Przybylski, Dariusz
Depypere, Maarten
Stiers, Pieter-Jan
Lambrechts, Dennis
Van Looveren, Riet
Torrekens, Sophie
Agostinis, Patrizia
Lambrechts, Diether
Maes, Frederik
Swinnen, Johan V.
Geris, Liesbet
Van Oosterwyck, Hans
Thienpont, Bernard
Carmeliet, Peter
Carmeliet, Geert
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https://doi.org/10.1038/s41586-020-2050-1Metadata
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Van Gastel, Nick, Stegen, Steve, Eelen, Guy, Schoors, Sandra, Carlier, Aurélie, Daniëls, Veerle W, Baryawno, Ninib, Przybylski, Dariusz, Depypere, Maarten, Stiers, Pieter-Jan, Lambrechts, Dennis, Van Looveren, Riet, Torrekens, Sophie, Sharda, Azeem, Agostinis, Patrizia, Lambrechts, Diether, Maes, Frederik, Swinnen, Johan V, Geris, Liesbet, Van Oosterwyck, Hans, Thienpont, Bernard, Carmeliet, Peter, Scadden, David T, and Carmeliet, Geert. "Lipid Availability Determines Skeletal Progenitor Cell Fate via SOX9." Nature (London) 579, no. 7797 (2020): 111-17.Abstract
The avascular nature of cartilage makes it a unique tissue, but whether and how the absence of nutrient supply regulates chondrogenesis remains 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 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 fatty acid oxidation, 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 FoxOs 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.Citable link to this page
https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37374197
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