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BBSome-dependent ciliary Hedgehog signaling governs cell fate in the white adipose tissue (scRNA-Seq)

ABSTRACT: BBSome-dependent ciliary Hedgehog signaling governs cell fate in the white adipose tissue (scRNA-Seq)

PROVIDER: PRJNA1069093 | ENA |

REPOSITORIES: ENA

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BSome-dependent ciliary Hedgehog signaling governs cell fate in the white adipose tissue

Project description:BSome-dependent ciliary Hedgehog signaling governs cell fate in the white adipose tissue

| PRJNA1069087 | ENA

BBSome-dependent ciliary Hedgehog signaling governs cell fate in the white adipose tissue (RNA-Seq)

Project description:BBSome-dependent ciliary Hedgehog signaling governs cell fate in the white adipose tissue (RNA-Seq)

| PRJNA1069088 | ENA

BBSome-dependent ciliary Hedgehog signaling governs cell fate in the white adipose tissue (scRNA-Seq)

Project description:The primary cilium has emerged as critical in regulating whole-body energy metabolism, as reflected in the Bardet-Biedl syndrome (BBS) where primary cilia dysfunction leads to obesity due to hyperphagia and white adipose tissue (WAT) remodeling. The regulation of cell fate and differentiation of adipocyte precursor cells (APCs) is key to maintaining WAT homeostasis during obesity. Using mice that recapitulated the BBS patient phenotype (Bbs8-/-), we demonstrate that primary cilia dysfunction reduces the stem-cell-like P1 APC subpopulation by inducing a phenotypic switch into a fibrogenic progenitor state, characterized by extracellular matrix (ECM) remodeling and upregulation of CD9. Single-cell RNA sequencing revealed a direct transition of stem-cell-like P1 cells into fibrogenic progenitors, bypassing the committed P2 cells. Ectopic ciliary Hedgehog signaling upon loss of BBS8 emerged as a central driver of the molecular changes in Bbs8-/- APCs, altering differentiation into adipocytes and lipid uptake. These findings unravel a novel role for primary cilia in governing APC fate, determining the delicate balance between adipogenesis and fibrogenesis. The identified molecular mechanisms provide insights into potential therapeutic targets for obesity.

2025-06-24 | GSE254258 | GEO

BBSome-dependent ciliary Hedgehog signaling governs cell fate in the white adipose tissue (RNA-Seq)

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BBS8-dependent ciliary Hedgehog signaling governs cell fate in the white adipose tissue.

Project description: Not available

| S-EPMC12489102 | biostudies-literature

BSome-dependent ciliary Hedgehog signaling governs cell fate in the white adipose tissue

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-06-24 | GSE254259 | GEO

BBS8-dependent ciliary Hedgehog signaling governs cell fate in the white adipose tissue

Project description: Not available

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Proteomic profiling of the ciliary Hedgehog response reveals coordinated exit of GPR161 and PKA

Project description:The primary cilium is a signaling compartment that interprets Hedgehog signals through changes of its protein, lipid and second messenger compositions. Here, we combine proximity labeling of cilia with quantitative mass spectrometry to unbiasedly profile the time-dependent alterations of the ciliary proteome in response to Hedgehog. This approach correctly identifies the three factors known to undergo Hedgehog-regulated ciliary redistribution and reveals two such additional proteins. First, we find that a regulatory subunit of the cAMP-dependent protein kinase (PKA) rapidly exits cilia together with the G protein-coupled receptor GPR161 in response to Hedgehog; and we propose that the GPR161/PKA module senses and amplifies cAMP signals to modulate ciliary PKA activity. Second, we identify the phosphatase Paladin as a cell type-specific regulator of Hedgehog signaling that enters primary cilia upon pathway activation. The broad applicability of quantitative ciliary proteome profiling promises a rapid characterization of ciliopathies and their underlying signaling malfunctions.

2021-04-07 | PXD024361 | Pride

Proteomic profiling of the ciliary Hedgehog response reveals coordinated exit of GPR161 and PKA

2021-04-07 | PXD024366 | Pride

Proteomic profiling of the ciliary Hedgehog response reveals coordinated exit of GPR161 and PKA

2021-04-07 | PXD024367 | Pride