Similar Datasets
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
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
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 | GSE196567 | GEO
Project description:Tcf21 functions as a rate-limiting factor during visceral adipose tissue development
| PRJNA805503 | ENA
Project description:Tcf21 functions as a rate-limiting factor during visceral adipose tissue development [ATAC- and RNA-Seq]
| PRJNA806352 | ENA
Project description:Tcf21 functions as a rate-limiting factor during visceral adipose tissue development [single-cell RNA-seq]
| PRJNA806353 | ENA
Project description:The visceral (VIS) and subcutaneous (SQ) fat pads are developmentally distinct white adipose tissue depots and contribute differently to inflammation and insulin resistance associated with obesity. The basic helix-loop-helix transcriptional regulator, transcription factor 21 (TCF21), is a marker gene for white adipose tissues and is abundantly expressed in VIS-derived adipose stem cells (ASCs), but not in SQ-derived ASCs. However, TCF21's role in regulating fat depot-specific gene expression and function is incompletely understood. Here, using siRNA-mediated Tcf21 knockdowns and lentiviral gene transfer of TCF21 in mouse ASCs, we demonstrate that TCF21 is required for the VIS ASC-specific expression of interleukin 6 (IL6), a key cytokine that contributes to the proinflammatory nature of VIS depots. Concurrently, TCF21 promotes MMP-dependent collagen degradation and type IV collagen deposition through the regulation of the extracellular matrix (ECM) modifiers, matrix metalloproteinase (MMP) 2, MMP13, and tissue inhibitor of MMP1 (TIMP1), as well as collagen type IV α1 chain (COL4A1) in VIS ASCs. We also found that although IL6 mediates the expression of Mmp13 and Timp1 in VIS ASCs, the TCF21-dependent expression of Mmp2 and Col4a1 is IL6-independent. These results suggest that TCF21 contributes to the proinflammatory environment in VIS fat depots and to active ECM remodeling of these depots by regulating IL6 expression and MMP-dependent ECM remodeling in a spatiotemporally coordinated manner.
| S-EPMC5925812 | biostudies-literature
Project description:Adipose tissue is a connective tissue specified for energy metabolism and endocrines, but functional differences between subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) have not been fully elucidated. To reveal the physiological role of SAT, we characterized in vivo tissue development and in vitro adipocyte differentiation. In a DNA microarray analysis of SAT and VAT in Wistar rats, functional annotation clusters of extracellular matrix (ECM)-related genes were found in SAT, and major ECM molecules expressed in adipose tissues were profiled. In a histological analysis and quantitative expression analysis, ECM expression patterns could be classified into two types: (i) a histogenesis-correlated type such as type IV and XV collagen, and laminin subunits, (ii) a high-SAT expression type such as type I, III, and V collagen and minor characteristic collagens. Type (i) was related to basal membrane and up-regulated in differentiated 3T3-L1 cells and in histogenesis at depot-specific timings. In contrast, type (ii) was related to fibrous forming and highly expressed in 3T3-L1 preadipocytes. Exceptionally, fibronectin was abundant in developed adipose tissue, although it was highly expressed in 3T3-L1 preadipocytes. The present study showed that adipose tissues site-specifically regulate molecular type and timing of ECM expression, and suggests that these characteristic ECM molecules provide a critical microenvironment, which may affect bioactivity of adipocyte itself and interacts with other tissues. It must be important to consider the depot-specific property for the treatment of obesity-related disorders, dermal dysfunction and for the tissue regeneration.
| S-EPMC4115194 | biostudies-literature
Project description:Background and aimsAccumulation of visceral adipose tissue is associated with hepatic inflammation and fibrosis, suggestive of its metabolic and inflammatory properties. We aimed to examine the histologic findings of visceral and subcutaneous adipose tissue and to associate these findings with clinical and radiologic characteristics in patients with cirrhosis.MethodsIncluded were 55 adults with cirrhosis who underwent liver transplantation from 3/2017-12/2018 and had an abdominal computed tomography (CT) scan within 6 months prior to transplant. Visceral-to-subcutaneous adipose tissue ratio (VSR) was calculated using visceral (VATI) and subcutaneous adipose tissue index (SATI) quantified by CT at the L3-vertebral level and normalized for height (cm2/m2). VAT (greater omentum), SAT (abdominal wall), and skeletal muscle (rectus abdominis) biopsies were collected at transplant.ResultsMajority of patients had VAT inflammation (71%); only one patient (2%) had SAT inflammation. Patients with VAT inflammation had similar median VATI (42 vs 41 cm2/m2), lower median SATI (64 vs 97 cm2/m2), and higher median VSR (0.63 vs 0.37, p = 0.002) than patients without inflammation. In univariable logistic regression, VSR was associated with VAT inflammation (OR 1.47, 95%CI 1.11-1.96); this association remained significant even after adjusting for age, sex, BMI, HCC, or MELD-Na on bivariable analyses.ConclusionIn patients with cirrhosis undergoing liver transplantation, histologic VAT inflammation was common, but SAT inflammation was not. Increased VSR was independently associated with VAT inflammation. Given the emerging data demonstrating the prognostic value of VSR, our findings support the value of CT-quantified VSR as a prognostic marker for adverse outcomes in the liver transplant setting.
| S-EPMC8815298 | biostudies-literature
Project description:Obesity and aging represent major health burdens to the global adult population. Both conditions promote the development of associated metabolic diseases such as insulin resistance. The visceral adipose tissue (VAT) is a site that becomes dysfunctional during obesity and aging, and plays a significant role during their pathophysiology. The changes in obese and aging VAT are now recognized to be partly driven by a chronic local inflammatory state, characterized by immune cells that typically adopt an inflammatory phenotype during metabolic disease. Here, we summarize the current knowledge on the immune cell landscape of the VAT during lean, obese, and aged conditions, highlighting their similarities and differences. We also briefly discuss possible linked mechanisms that fuel obesity- and age-associated VAT dysfunction.
| S-EPMC7243349 | biostudies-literature