biostudies-literatureTavares AHNational Institute of Diabetes and Digestive and Kidney DiseasesNIDDK NIH HHSNational Institutes of HealthBoston Nutrition Obesity Research Center, Boston University110563https://www.ebi.ac.uk/biostudies/studies/S-EPMC12423405biostudies-literatureUnknown301(9)White adipose tissue (WAT) fibrosis is a major determinant of obesity-induced cardiometabolic dysfunction and is characterized by excessive extracellular matrix deposition and myofibroblast activation. Transforming growth factor (TGF)-β1 is a profibrotic cytokine that potently induces myofibroblast activation in adipocyte stem cells (ASCs). How TGF-β1 orchestrates ASC activation in WAT fibrosis is not completely understood. We identified FOXS1, a member of the forkhead box transcription factor superfamily, as a transcriptional target of TGF-β1 signaling in primary human WAT ASC (hASC). FOXS1 potentiated TGF-β1-dependent upregulation of several myofibroblast genes (e.g. Acta2, Col1a1, Fn1, and Il11) in 10T1/2 fibroblasts. FOXS1 also attenuated the induction of several adipogenic factors (e.The Journal of biological chemistryTGF-β1-dependent expression of FOXS1 attenuates adipogenic potential and enhances a myofibroblast cellular phenotype.PMC12423405P30 DK046200R01DK132080P30DK046200R01 DK134534T32DK007201R01 DK132080T32 DK007201R01DK134534Layne MDZheng JTavares AHRabhi NConnelly SPMaksat DfalseTGF-β1-dependent expression of FOXS1 attenuates adipogenic potential and enhances a myofibroblast cellular phenotype.White adipose tissue (WAT) fibrosis is a major determinant of obesity-induced cardiometabolic dysfunction and is characterized by excessive extracellular matrix deposition and myofibroblast activation. Transforming growth factor (TGF)-β1 is a profibrotic cytokine that potently induces myofibroblast activation in adipocyte stem cells (ASCs). How TGF-β1 orchestrates ASC activation in WAT fibrosis is not completely understood. We identified FOXS1, a member of the forkhead box transcription factor superfamily, as a transcriptional target of TGF-β1 signaling in primary human WAT ASC (hASC). FOXS1 potentiated TGF-β1-dependent upregulation of several myofibroblast genes (e.g. Acta2, Col1a1, Fn1, and Il11) in 10T1/2 fibroblasts. FOXS1 also attenuated the induction of several adipogenic factors (e.2025-01-01T00:00:00Z2025 Aug2026-06-03T02:51:36.712Z2026-04-23T03:11:57.747ZS-EPMC124234054077438610.1016/j.jbc.2025.110563