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000281535 1001_ $$00009-0008-0336-8835$$aSieckmann, Katharina$$b0
000281535 245__ $$aBBS8-dependent ciliary Hedgehog signaling governs cell fate in the white adipose tissue.
000281535 260__ $$a[London]$$bNature Publishing Group UK$$c2025
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000281535 520__ $$aThe primary cilium plays a crucial role in regulating whole-body energy metabolism, as reflected in Bardet-Biedl syndrome (BBS), where ciliary dysfunction leads to obesity due to hyperphagia and white adipose tissue (WAT) remodeling. Regulation of the fate and differentiation of adipocyte precursor cells (APCs) is essential for maintaining WAT homeostasis during obesity. Using Bbs8-/- mice that recapitulate the BBS patient phenotype, we demonstrate that primary cilia dysfunction reduces the stem-cell-like P1 APC subpopulation by inducing a phenotypic switch to a fibrogenic progenitor state. This switch is characterized by extracellular matrix (ECM) remodeling and upregulation of the fibrosis marker CD9, even before the onset of obesity. Single-cell RNA sequencing reveals a direct transition of P1 APCs into fibrogenic progenitors, bypassing the committed P2 progenitor state. Ectopic ciliary Hedgehog signaling upon loss of BBS8 appears as a central driver of the molecular changes in Bbs8-/- APCs, altering their differentiation into adipocytes and promoting their lipid uptake. These findings unravel a novel role for primary cilia in governing APC fate by determining the balance between adipogenesis and fibrogenesis, and suggest potential therapeutic targets for obesity.
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000281535 650_7 $$2Other$$aAdipose Tissue
000281535 650_7 $$2Other$$aBBS
000281535 650_7 $$2Other$$aCell Fate
000281535 650_7 $$2Other$$aCilia
000281535 650_7 $$2NLM Chemicals$$aHedgehog Proteins
000281535 650_7 $$2NLM Chemicals$$aMicrotubule-Associated Proteins
000281535 650_2 $$2MeSH$$aAnimals
000281535 650_2 $$2MeSH$$aAdipose Tissue, White: metabolism
000281535 650_2 $$2MeSH$$aAdipose Tissue, White: cytology
000281535 650_2 $$2MeSH$$aAdipose Tissue, White: pathology
000281535 650_2 $$2MeSH$$aMice
000281535 650_2 $$2MeSH$$aHedgehog Proteins: metabolism
000281535 650_2 $$2MeSH$$aHedgehog Proteins: genetics
000281535 650_2 $$2MeSH$$aSignal Transduction
000281535 650_2 $$2MeSH$$aCilia: metabolism
000281535 650_2 $$2MeSH$$aMice, Knockout
000281535 650_2 $$2MeSH$$aCell Differentiation
000281535 650_2 $$2MeSH$$aAdipogenesis
000281535 650_2 $$2MeSH$$aBardet-Biedl Syndrome: metabolism
000281535 650_2 $$2MeSH$$aBardet-Biedl Syndrome: genetics
000281535 650_2 $$2MeSH$$aBardet-Biedl Syndrome: pathology
000281535 650_2 $$2MeSH$$aObesity: metabolism
000281535 650_2 $$2MeSH$$aObesity: genetics
000281535 650_2 $$2MeSH$$aObesity: pathology
000281535 650_2 $$2MeSH$$aAdipocytes: metabolism
000281535 650_2 $$2MeSH$$aAdipocytes: cytology
000281535 650_2 $$2MeSH$$aMicrotubule-Associated Proteins: metabolism
000281535 650_2 $$2MeSH$$aMicrotubule-Associated Proteins: genetics
000281535 693__ $$0EXP:(DE-2719)PRECISE-20190321$$5EXP:(DE-2719)PRECISE-20190321$$ePlatform for Single Cell Genomics and Epigenomics at DZNE  University of Bonn$$x0
000281535 7001_ $$aWinnerling, Nora$$b1
000281535 7001_ $$aSilva Ribeiro, Dalila Juliana$$b2
000281535 7001_ $$00000-0002-9317-9171$$aYüksel, Seniz$$b3
000281535 7001_ $$00009-0004-3649-2024$$aKardinal, Ronja$$b4
000281535 7001_ $$aSteinheuer, Lisa Maria$$b5
000281535 7001_ $$00009-0003-1279-2842$$aFrechen, Fabian$$b6
000281535 7001_ $$aCorrêa, Luis Henrique$$b7
000281535 7001_ $$aSchermann, Geza$$b8
000281535 7001_ $$aKlausen, Christina$$b9
000281535 7001_ $$aBlank-Stein, Nelli$$b10
000281535 7001_ $$0P:(DE-2719)9001500$$aSchulte-Schrepping, Jonas$$b11$$udzne
000281535 7001_ $$0P:(DE-2719)2813660$$aOsei-Sarpong, Collins$$b12
000281535 7001_ $$0P:(DE-2719)2812750$$aBecker, Matthias$$b13
000281535 7001_ $$0P:(DE-2719)9001512$$aBonaguro, Lorenzo$$b14
000281535 7001_ $$0P:(DE-2719)2812219$$aBeyer, Marc$$b15
000281535 7001_ $$aMay-Simera, Helen Louise$$b16
000281535 7001_ $$00000-0002-5932-4849$$aZurkovic, Jelena$$b17
000281535 7001_ $$00000-0001-5161-2558$$aThiele, Christoph$$b18
000281535 7001_ $$00000-0002-7217-2755$$aThurley, Kevin$$b19
000281535 7001_ $$00000-0001-7704-7921$$aSorokin, Lydia$$b20
000281535 7001_ $$00000-0001-5975-7815$$aRuiz de Almodovar, Carmen$$b21
000281535 7001_ $$00000-0003-2318-2356$$aMass, Elvira$$b22
000281535 7001_ $$0P:(DE-2719)9002895$$aWachten, Dagmar$$b23
000281535 773__ $$0PERI:(DE-600)1467419-1$$a10.1038/s44318-025-00524-y$$gVol. 44, no. 19, p. 5315 - 5336$$n19$$p5315 - 5336$$tThe EMBO journal$$v44$$x0261-4189$$y2025
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