Single-cell RNA sequencing of coronary perivascular adipose tissue
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE233870 | GEO | 2023/09/15
REPOSITORIES: GEO
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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: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: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 | 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:Inflammatory crosstalk between perivascular adipose tissue and and blood vessel wall may contribute to atherosclerosis pathogenesis, and exhibits more pro-inflammatory than adipogenic phenotype than subcutaneous adipocytes. To identify a genomic basis for biologic differences, we performed genome-wide expression to identiy expression genes differentially regulated between perivascular and subcutaneous adipocytes.for biologic differences. We performed global gene expression analyses on in vitro differentiated adipocytes from human left coronary artery perivascular adipose tissue and subcutaneous adipose tissues derived from unrelated donors who were non-obese and did not have any known metabolic or atherosclerotic disease.
2013-03-15 | E-GEOD-45169 | biostudies-arrayexpress
Project description:Perivascular adipose tissue (PVAT) is thought to play a role in vascular homeostasis and in the pathogenesis of diseases of large vessels. We tested the hypothesis that locally restricted transcriptional profiles characterize the PVAT localized at the site of the obstruction of the abdominal aorta in peripheral artery disease (PAD) patients. By a genome-wide approach and a paired-samples design, we investigated the PVAT transcriptome of 11 PAD patients with occlusive and with stenotic abdominal aortic lesions. We performed a data adjustment step using the DaMiRseq R/Bioconductor package, to remove the effect of confounders as produced by high-throughput gene expression techniques. We compared PVAT of the distal versus the proximal aorta of each patient to limit the effect of inter-individual variability, using the limma R/Bioconductor package. We did not find consistent differences in PVAT gene expression clearly distinguishing the two PVAT of the same patient. However, we found significant differences by comparing patients with total occlusive versus those with stenotic abdominal aortic lesions. We dissected putative mechanisms associated with PVAT involvement in PAD patients with total occlusive and with stenotic abdominal aorta lesions through a functional enrichment network analysis: cholesterol, sterol and alcohol biosynthetic process were enriched in patients with total occlusive lesions, whereas pathways recalling the structure maintenance and remodeling of the vessels were associated with patients with stenotic lesions. Our results would suggest that the PVAT transcriptome at the distal aorta site is associated with the degree of the atherosclerotic burden in PAD patients and that this effect can probably account for a diffuse (systemic) process affecting homogenously the PVATs spanning along the distal aorta rather than a singular specific trait.
2020-04-20 | GSE136822 | GEO
Project description:Most blood vessels are surrounded with perivascular adipose tissue (PVAT), which is a unique adipose tissue that plays critical roles in vascular physiology and pathophysiology. PVAT displays regional differences that impact vascular homeostasis. Angiotensin II (Ang II) is the main biological active effector of the renin-angiotensin-aldosterone system (RAAS), which has been extensively studied in the vascular biology. However, the effects of Ang II on PVAT are limited explored and remain to be elucidated. In this study, we systematically investigated the regional heterogeneity of three portions of aortic PVAT, i.e., ascending thoracic aortic PVAT (ATA-PVAT), descending thoracic aortic PVAT (DTA-PVAT), and abdominal aortic PVAT (AA-PVAT), and their responses to 7-day Ang II infusion using RNA sequencing. We found that AA-PVAT is clearly distinguished from both ATA-PVAT and DTA-PVAT, with significantly down-regulated oxidative phosphorylation and up-regulated inflammatory response pathways. Furthermore, AA-PVAT expressed lower levels of brown adipocyte marker genes, such as Ucp1, Cidea, Cox8b, Dio2 and Pgc1α, but expressed higher levels of proinflammatory genes, such as Ccl2, Il1β and Tnfα, and components of the RAAS, including Agt, Ace and Agtr1α. Ang II infusion significantly down-regulated oxidative phosphorylation in all aortic PVAT and significantly up-regulated inflammatory response specifically in ATA-PVAT and DTA-PVAT. Moreover, ATA-PVAT was most responsive to Ang II induced inflammation. We further used a mitoNEET (a.k.a. CDGSH iron sulfur domain 1 protein) transgenic mouse model that exhibited a more brown adipose tissue (BAT)-like phenotype in aortic PVAT, as indicated by elevated expression levels of brown adipocyte marker genes, and confirmed that a more BAT-like phenotype of aortic PVAT could counterbalance Ang II induced inflammatory and oxidative effects.
2025-01-21 | GSE194224 | 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.
2011-08-23 | GSE28440 | GEO
Project description:We are exploring pathways influenced by short-term dietary methionine restriction (MR) in thoracic aorta and associated perivascular adipose tissue (PVAT) from obese C57BL/6J male mice around 26 weeks of age. Mice were fed 60% high fat diet (HFD) until they were obese, experimental mice were given 60% HFD with 0.12% methionine for 3, 5, and 10 days while the control group maintained a 60% HFD with 0.86% methionine. All mice were euthanized on the same day, then thoracic aorta was harvested, the PVAT was removed, and both sample types were prepared and analyzed separately. Three mice per group were assessed with LC-MS/MS. MR diet induced lean phenotype in PVAT, which was observed histologically, and we hypothesized that changes in lipid metabolism and mitochondrial bioenergetics mediated this response.
2025-04-07 | PXD051504 | Pride