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Tcf21 functions as a rate-limiting factor during visceral adipose tissue development

ABSTRACT: Tcf21 functions as a rate-limiting factor during visceral adipose tissue development

PROVIDER: PRJNA805503 | ENA |

REPOSITORIES: ENA

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Tcf21 functions as a rate-limiting factor during visceral adipose tissue development [ATAC- and RNA-Seq]

Project description:The location of visceral adipose tissue (VAT) suggests specific developmental regulation. Our lineage-tracing study identified the specific expression of Tcf21 in VAT progenitor cells (PCs). Tcf21 lineage PCs (LPs) actively differentiate into adipocytes during development but not in adulthood. Bulk RNAseq identified dynamic gene expression of Tcf21 LPs, including enrichment of pro-mitotic and pro-adipogenic genes during development and increased expression of a set of fibrotic genes in obese mice. ATACseq revealed chromatin remodeling that was highly correlated with gene expression dynamics. Using a novel computational approach via integrative analysis of gene expression and chromatin accessibility profiles, an underlying gene regulatory network was reconstructed. Single-cell RNAseq identified subpopulations of Tcf21 LPs including mesothelial and interstitial subpopulations. Using an inducible Tcf21 knockout line, we identified that loss of Tcf21 promoted the adipogenesis and developmental progress of Tcf21 LPs, leading to improved metabolic health of mice after HFD challenge. Mechanistic studies showed that Tcf21 mainly targets enhancers, and the inhibitory effect of Tcf21 on adipogenesis is at least partially through the increasing Dlk1 expression.

2023-02-28 | GSE196568 | GEO

Tcf21 functions as a rate-limiting factor during visceral adipose tissue development [single-cell RNA-seq]

2023-02-28 | GSE196567 | GEO

Tcf21 functions as a rate-limiting factor during visceral adipose tissue development [ATAC- and RNA-Seq]

Project description:Tcf21 functions as a rate-limiting factor during visceral adipose tissue development [ATAC- and RNA-Seq]

| PRJNA806352 | ENA

Tcf21 functions as a rate-limiting factor during visceral adipose tissue development [single-cell RNA-seq]

Project description:Tcf21 functions as a rate-limiting factor during visceral adipose tissue development [single-cell RNA-seq]

| PRJNA806353 | ENA

Tcf21 marks visceral adipose mesenchymal progenitors and functions as a rate-limiting factor during visceral adipose tissue development.

Project description:Distinct locations of different white adipose depots suggest anatomy-specific developmental regulation, a relatively understudied concept. Here, we report a population of Tcf21 lineage cells (Tcf21 LCs) present exclusively in visceral adipose tissue (VAT) that dynamically contributes to VAT development and expansion. During development, the Tcf21 lineage gives rise to adipocytes. In adult mice, Tcf21 LCs transform into a fibrotic or quiescent state. Multiomics analyses show consistent gene expression and chromatin accessibility changes in Tcf21 LC, based on which we constructed a gene-regulatory network governing Tcf21 LC activities. Furthermore, single-cell RNA sequencing (scRNA-seq) identifies the heterogeneity of Tcf21 LCs. Loss of Tcf21 promotes the adipogenesis and developmental progress of Tcf21 LCs, leading to improved metabolic health in the context of diet-induced obesity. Mechanistic studies show that the inhibitory effect of Tcf21 on adipogenesis is at least partially mediated via Dlk1 expression accentuation.

| S-EPMC10208561 | biostudies-literature

Tcf21 functions as a rate-limiting factor during visceral adipose tissue development

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

2023-02-28 | GSE196569 | GEO

Identification of BBX proteins as rate-limiting co-factors of HY5

Project description:Identification of BBX proteins as rate-limiting co-factors of HY5

| PRJNA564640 | ENA

Brown Adipose Tissue (BAT) in Visceral Fat Depot

Project description:Case story. A patient with massive infiltration of the visceral adipose tissue depot by BAT in a patient with a catecholamine secreting paraganglioma. BAT tissue was identified by protein expression of UCP1 (western blotting and immunostaining) The goal of the study is to identify patterns of gene expression in BAT containing visceral fat compared to the patient's own subcutanous fat which did not express BAT. For comparison a pool of mRNA isolated from visceral fat from obese subjects was used. Patient Case, Gene expression array from a biopsy from the patient's visceral fat and a biopsy from the subcutaneous fat compared to one array of mRNA from the visceral depot pooled from a group of obese subjects

2014-08-12 | E-GEOD-49795 | biostudies-arrayexpress

Visceral adipose tissue macrophage subsets

Project description:Visceral adipose tissue macrophage subsets

| PRJNA484897 | ENA

Adipose Precursor HO-1 prevents healthy visceral adipose tissue expansion during obesity[II]

Project description:Excessive accumulation of white adipose tissue (WAT) is a hallmark of obesity. The expansion of WAT in obesity involves proliferation and differentiation of adipose precursors (APs), however, the underlying molecular mechanisms remain unclear. Here, we identify Heme Oxygenase-1 (HO-1) as selectively being upregulated in the AP fraction of WAT, upon high-fat diet (HFD) feeding. Specific conditional deletion of HO-1 in APs of Hmox1fl/fl-Pdgfra Cre mice enhanced HFD-dependent visceral AP proliferation and differentiation, upstream of Cebpα and PPARγ. Opposite effects on human preadipocyte proliferation and differentiation in vitro were observed following HO-1 overexpression. Mechanistically, HO-1 acts upstream of AKT2 via ROS thresholding in mitochondria. Deletion of HO-1 in APs is sufficient to lower blood glucose, insulin and free fatty acid levels as well as liver steatosis during obesity, an effect not seen when HO-1 was conditionally deleted at later stages of adipogenesis using AdipoQ-Cre. Together, our data identify HO-1 as a diet-induced regulator limiting visceral adipose tissue hyperplasia during obesity.

2017-03-08 | GSE80147 | GEO

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