Single-cell view and a novel protective macrophage subset in perivascular adipose tissue (PVAT) in T2DM
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE275779 | GEO | 2024/08/27
REPOSITORIES: GEO
Similar Datasets
Project description:Single-cell view and a novel protective macrophage subset in perivascular adipose tissue (PVAT) in T2DM
| PRJNA1152965 | ENA
Project description:Brown adipose tissue can expend large amounts of energy and thus increasing its amount or activity is a promising therapeutic approach to combat metabolic disease. In humans, major deposits of brown fat cells are found intimately associated with large blood vessels, corresponding to perivascular adipose tissue (PVAT). However, the cellular origins of PVAT are poorly understood. We applied single cell transcriptomic analyses, ex vivo adipogenesis assays, and genetic fate mapping to determine the identity of perivascular adipocyte progenitors. In mice, we found that thoracic PVAT develops from a fibroblastic lineage, consisting of progenitor cells (Pdgfra+; Ly6a+; Pparg-) and preadipocytes (Pdgfra+; Ly6a+; Pparg+). Progenitor and preadipocyte cells in PVAT shared transcriptional similarity with analogous cell types in white adipose tissue, pointing towards a conserved hierarchical structure of adipose lineage cells. Interestingly, the aortic adventitia of adult animals contained a novel population of adipogenic smooth muscle cells (SMCs) (Myh11+; Pdgfra-; Pparg+) that contributed to perivascular adipocyte formation. Similarly, human PVAT contained presumptive fibroblastic and SMC-like adipocyte progenitors, as revealed by single nucleus RNAseq. Taken together, these studies define distinct populations of progenitor cells for thermogenic PVAT, providing a foundation for developing strategies to augment brown fat activity.
2021-04-01 | GSE166355 | GEO
Project description:Brown adipose tissue can expend large amounts of energy and thus increasing its amount or activity is a promising therapeutic approach to combat metabolic disease. In humans, major deposits of brown fat cells are found intimately associated with large blood vessels, corresponding to perivascular adipose tissue (PVAT). However, the cellular origins of PVAT are poorly understood. We applied single cell transcriptomic analyses, ex vivo adipogenesis assays, and genetic fate mapping to determine the identity of perivascular adipocyte progenitors. In mice, we found that thoracic PVAT develops from a fibroblastic lineage, consisting of progenitor cells (Pdgfra+; Ly6a+; Pparg-) and preadipocytes (Pdgfra+; Ly6a+; Pparg+). Progenitor and preadipocyte cells in PVAT shared transcriptional similarity with analogous cell types in inguinal white adipose tissue (IWAT), pointing towards a conserved hierarchical structure of adipose lineage cells. Interestingly, the aortic adventitia of adult animals contained a novel population of adipogenic smooth muscle cells (SMCs) (Myh11+; Pdgfra-; Pparg+) that contributed to perivascular adipocyte formation. Similarly, human PVAT contained presumptive fibroblastic and SMC-like adipocyte progenitors, as revealed by single nucleus RNAseq. Taken together, these studies define distinct populations of progenitor cells for thermogenic PVAT, providing a foundation for developing strategies to augment brown fat activity
2021-04-01 | GSE164527 | GEO
Project description:Defining the lineage of thermogenic perivascular adipose tissue [Thoracic PVAT]
| PRJNA700602 | ENA
Project description:Perivascular adipose tissue (PVAT) is vital for vascular homeostasis and PVAT dysfunction is associated with increased atherosclerotic plaque burden.
2023-09-15 | GSE233870 | GEO
Project description:Thoracic perivascular adipose tissue (PVAT) is a unique adipose depot that likely influences vascular function and susceptibility to pathogenesis in obesity and metabolic syndrome. Surprisingly, PVAT has been reported to share characteristics of both brown and white adipose, but a detailed direct comparison to interscapular brown adipose tissue (BAT) has not been performed. Here we show by full genome DNA microarray analysis that global gene expression profiles of PVAT are virtually identical to BAT, with equally high expression of Ucp-1, Cidea and other genes known to be uniquely or very highly expressed in BAT. PVAT and BAT also displayed nearly identical phenotypes upon immunohistochemical analysis, and electron microscopy confirmed that PVAT contained multilocular lipid droplets and abundant mitochondria. Compared to white adipose tissue (WAT), PVAT and BAT from C57BL/6 mice fed a high fat diet for 13 weeks had markedly lower expression of immune cell-enriched mRNAs, suggesting resistance to obesity-induced inflammation. Indeed, staining of BAT and PVAT for macrophage markers (F4/80, CD68) in obese mice showed virtually no macrophage infiltration, and FACS analysis of BAT confirmed the presence of very few CD11b+/CD11c+ macrophages in BAT (1.0%) in comparison to WAT (31%). In summary, murine PVAT from the thoracic aorta is virtually identical to interscapular BAT, is resistant to diet-induced macrophage infiltration, and thus may play an important role in protecting the vascular bed from thermal and inflammatory stress. 8-week-old male C57BL6/J mice were fed a normal (ND) or high fat diet (HFD) (Research Diets 12451, 45 kcal% fat) for 13 weeks. Mice were then euthanized and four different adipose depots were harvested for RNA analysis: perivascular fat from the lesser curvature of the aortic arch (PVAT), interscapular brown adipose (BAT), inguinal adipose tissue (SAT), and epididymal adipose tissue (VAT). 250 ng total RNA pooled from two mice was used for cDNA synthesis; 3 biological replicates per tissue and diet were performed for a total of 24 hybridizations.
2011-08-22 | E-GEOD-28440 | biostudies-arrayexpress
Project description:Defining the lineage of thermogenic perivascular adipose tissue [PVAT v IWAT]
| PRJNA691062 | ENA
Project description:Brown adipose tissue can expend large amounts of energy and thus increasing its amount or activity is a promising therapeutic approach to combat metabolic disease. In humans, major deposits of brown fat cells are found intimately associated with large blood vessels, corresponding to perivascular adipose tissue (PVAT). However, the cellular origins of PVAT are poorly understood. We applied single cell transcriptomic analyses, ex vivo adipogenesis assays, and genetic fate mapping to determine the identity of perivascular adipocyte progenitors. In mice, we found that thoracic PVAT develops from a fibroblastic lineage, consisting of progenitor cells (Pdgfra+; Ly6a+; Pparg-) and preadipocytes (Pdgfra+; Ly6a+; Pparg+). Progenitor and preadipocyte cells in PVAT shared transcriptional similarity with analogous cell types in white adipose tissue, pointing towards a conserved hierarchical structure of adipose lineage cells. Interestingly, the aortic adventitia of adult animals contained a novel population of adipogenic smooth muscle cells (SMCs) (Myh11+; Pdgfra-; Pparg+) that contributed to perivascular adipocyte formation. Similarly, human PVAT contained presumptive fibroblastic and SMC-like adipocyte progenitors, as revealed by single nucleus RNAseq. Taken together, these studies define distinct populations of progenitor cells for thermogenic PVAT, providing a foundation for developing strategies to augment brown fat activity
2021-04-01 | GSE164525 | GEO
Project description:Brown adipose tissue can expend large amounts of energy and thus increasing its amount or activity is a promising therapeutic approach to combat metabolic disease. In humans, major deposits of brown fat cells are found intimately associated with large blood vessels, corresponding to perivascular adipose tissue (PVAT). However, the cellular origins of PVAT are poorly understood. We applied single cell transcriptomic analyses, ex vivo adipogenesis assays, and genetic fate mapping to determine the identity of perivascular adipocyte progenitors. In mice, we found that thoracic PVAT develops from a fibroblastic lineage, consisting of progenitor cells (Pdgfra+; Ly6a+; Pparg-) and preadipocytes (Pdgfra+; Ly6a+; Pparg+). Progenitor and preadipocyte cells in PVAT shared transcriptional similarity with analogous cell types in white adipose tissue, pointing towards a conserved hierarchical structure of adipose lineage cells. Interestingly, the aortic adventitia of adult animals contained a novel population of adipogenic smooth muscle cells (SMCs) (Myh11+; Pdgfra-; Pparg+) that contributed to perivascular adipocyte formation. Similarly, human PVAT contained presumptive fibroblastic and SMC-like adipocyte progenitors, as revealed by single nucleus RNAseq. Taken together, these studies define distinct populations of progenitor cells for thermogenic PVAT, providing a foundation for developing strategies to augment brown fat activity
2021-04-01 | GSE164526 | GEO
Project description:Recent investigations raise the possibility that senescent immune cells may fuel vascular damage by perivascular adipose tissue (PVAT) dysfunction, as immune cell infiltration in PVAT increases substantially in the development of vascular disease compared to the healthy state and leads to changes in PVAT-derived effector cytokine levels that comprise vascular biology.Though evidence revealed possible cross-talk among immune cells, PVAT and vasculature, it is less clear if senescent immune cells or a particular cell subset may induce PVAT dysfunction and further impair vascular biology during type 2 diabtes (T2DM). NLRP3 inflammasome plays a critical role in inflammatory response as a major component of innate immunity, it provides a molecular platform that responds to a variety of stimuli, initiating sterile inflammation cascade.Furthermore, there is evidence that NLRP3 inflammasome can be activated by sensing danger-associated molecular patterns (DAMPs), which in turn promotes age-related thymic demise and T cell senescence, implicating its potential role in immunosenescence. Here, we employed WT and Nlrp3 KO mice to develop T2DM, and implanted the splenocytes isolated from WT, Nlrp3 KO, WT-T2DM, Nlrp3 KO-T2DM mice that were modeled for 4 months to 3-month-old WT mice. Then, we explored the differentially expressed genes of PVAT in recipient mice implanted with splenocytes and evaluate immune infiltration of PVAT.
2023-08-31 | GSE242021 | GEO