Beiging of perivascular adipose tissue regulates its inflammation and vascular remodeling
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ABSTRACT:
PROVIDER: PRJNA850433 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19737665_1.fastq.gz | Fastqsanger.gz | |||
| SRR19737665_2.fastq.gz | Fastqsanger.gz | |||
| SRR19737666_1.fastq.gz | Fastqsanger.gz | |||
| SRR19737666_2.fastq.gz | Fastqsanger.gz | |||
| SRR19737667_1.fastq.gz | Fastqsanger.gz |
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Project description:Although inflammation plays critical roles in the development of atherosclerosis, its regulatory mechanisms remain incompletely understood. Perivascular adipose tissue (PVAT) has been reported to undergo inflammatory changes in response to vascular injury. Here, we showed that vascular injury induced the beiging (brown adipose tissue-like phenotype change) of PVAT, which fine-tunes inflammatory response and thus vascular remodeling as a protective mechanism. In a mouse model of endovascular injury, macrophages accumulated in PVAT, causing beiging phenotype change. Inhibition of PVAT beiging by genetically silencing PRDM16, a key regulator to beiging, exacerbated inflammation and vascular remodeling following injury. Conversely, activation of PVAT beiging attenuated inflammation and pathological vascular remodeling. Single-cell RNA sequencing revealed that beige adipocytes abundantly expressed neuregulin 4 (Nrg4) which critically regulated alternative macrophage activation. Importantly, significant beiging was observed in the diseased aortic PVAT in patients with acute aortic dissection. Taken together, vascular injury induced the beiging of adjacent PVAT with macrophage accumulation, where NRG4 secreted from the beige PVAT facilitated alternative activation of macrophages, leading to the resolution of vascular inflammation. Our study demonstrated the pivotal roles of PVAT in vascular inflammation and remodeling and will open a new avenue for treating atherosclerosis.
2022-06-21 | GSE206399 | GEO
Project description:Beige adipocytes are induced by cold temperatures or β3-adrenergic receptor (Adrb3) agonists. They create heat through glucose and fatty acid (FA) oxidation, conferring metabolic benefits. The distinct and shared mechanisms by which these treatments induce beiging are unknown. Here, we performed single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) on adipose tissue from mice exposed to cold or an Adrb3 agonist to identify cellular and chromatin accessibility dynamics during beiging. Both stimuli induce chromatin remodeling that influence vascularization and inflammation in adipose. Beige adipocytes from cold-exposed mice have increased accessibility at genes regulating glycolytic processes, whereas Adrb3 activation increases cAMP responses. While both thermogenic stimuli increase accessibility at genes regulating thermogenesis, lipogenesis, and beige adipocyte development, the kinetics and magnitudes of the changes are distinct for the stimuli. Accessibility changes at lipogenic genes are linked to functional changes in lipid composition of adipose. Both stimuli tend to decrease the proportion of palmitic acids, a saturated FA in adipose. However, Adrb3 activation increases the proportion of monounsaturated FAs, whereas cold increases the proportion of polyunsaturated FAs. These findings reveal common and distinct mechanisms of cold and Adrb3 induced beige adipocyte biogenesis, and identify unique functional consequences of manipulating these pathways in vivo.
2022-06-06 | GSE185377 | GEO
Project description:Remodeling of gene regulatory networks underlying thermogenic stimuli-induced adipose beiging
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Project description:Obesity-driven pathological expansion of white adipose tissue (WAT) is a key driver of endothelial dysfunction. Contrary to this paradigm, early vascular alterations associated with over nutrition also exacerbate AT dysfunction. To dissect this complex cause and consequence relationship, here we perform a single-cell transcriptomics screen to generate a detailed landscape of endothelial heterogeneity and vascular alterations in murine model of obesity. Given the differences in ontogeny and function of distinct WAT depots, we demarcate key differences in subcutaneous and visceral WAT vasculature. In addition to descriptive taxonomy, we perform in-depth validation and characterization of our in silico data. We identify a sWAT specific fenestrated endothelial cell subtype, which is drastically reduced in obese conditions. This reduction was associated with a decrease in VEGFA expressing perivascular cells. The novel endothelial subtypes provide a basis for future research and new directions for therapeutic interventions.
2023-05-26 | E-MTAB-12855 | biostudies-arrayexpress
Project description:The induction of beige adipocytes in white adipose tissue (WAT), also known as WAT beiging, improves glucose and lipid metabolism. However, the regulation of WAT beiging at the posttranscriptional level remains elusive. Here, we report that METTL3, the methyltransferase of N6-methyladenosine (m6A) mRNA modification, is induced during WAT beiging in mice. Adipose-specific depletion of Mettl3 gene undermines WAT beiging. Transcriptomic analysis of m6A modifications and mRNA expression level reveals global reduction of m6A-modified mRNAs in Mettl3-depleted beige adipose tissue. In particular, METTL3-catalyzed m6A installation on Krüppel-like factor 9 (Klf9) mRNA prevents its degradation. We further demonstrate that the m6A reader protein IGF2BP3 mediates the stabilization of m6A-modified Klf9 mRNA. Overexpressioin of KLF9 protein reverses the impaired WAT beiging elicited by Mettl3 deletion. These findings uncover a novel epitranscriptional mechanism in WAT beiging and identify METTL3-KLF9 axis as a potential therapeutic target for obesity-associated disorders.
2023-02-03 | GSE178884 | GEO
Project description:Perivascular adipose tissue (PVAT) is vital for vascular homeostasis and PVAT dysfunction is associated with increased atherosclerotic plaque burden.
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Project description:Adipose tissue beiging refers to a process through which beige adipocytes emerge in classical white adipose tissue depots. Beige adipocytes dissipate chemical energy and secrete adipokines like classical brown adipocytes to improve systemic metabolism, which offers benefits for people with obesity and metabolic diseases. Cold exposure and β3-adrenergic receptor (AR) agonist treatment are two commonly used stimuli for increasing beige adipocytes in mice, but their underlying biological processes are different. Transcriptional analysis of inguinal white adipose tissue (iWAT) has revealed that changes in extracellular matrix (ECM) pathway genes are specific to cold exposure. Hyaluronic acid (HA), a non-sulfated linear polysaccharide produced by nearly all cells, is one of the most common components of ECM. We found that cold exposure significantly increases iWAT HA levels while β3-AR agonist CL316,243 fails to do so. Increasing HA level in iWAT by Has2 overexpression significantly increases cold-induced adipose tissue beiging; in contrast, decreasing HA by Spam1 overexpression, which encodes a hyaluronidase that digests HA, significantly decreases cold-induced iWAT beiging. All of these data implicate a role of HA in promoting adipose tissue beiging that is unique to cold exposure. Given the failure of β3-AR agonists in clinical trials for obesity and metabolic diseases, increasing HA could serve as a new approach to recruiting more beige adipocytes to combat metabolic diseases.
2024-08-01 | GSE268781 | GEO
Project description:Recent researches identified the existence of adipose derived stem cells (ADSCs) in adipose tissue. Perivascular ADSCs (PV-ADSCs) locate around vasculatures and can differentiate into vascular lineages. However, the detailed cellular heterogeneity within PV-ADSCs has not been investigated. Therefore, we performed single-cell profiling of subcutaneous (S-) and perivascular (PV-) ADSCs from wild-type and obese mice. After referring to the clustering strategies from other ADSCs’ single-cell data, we provided a more comprehensive picture and trajectory, especially for PV-ADSCs. Both single-cell analysis and in vitro experiments revealed that S-ADSCs from obese mice had impaired abilities of cell migration and proliferation compared to wild-type S-ADSCs. PV-ADSCs have distinctively intrinsic properties. We uncovered 4 subpopulations of PV-ADSCs including Dpp4+, Col4a2+, Clec11a+ and Sult1e1+ cells. Notably, the differentiative function of PV-ADSCs towards vascular lineages was mainly attributed to the existence of Clec11a+ subpopulation, which highly expressed Mgp. The present study provided an integrative view of the ADSCs’ variance from the perspective of origins and obesity.
2022-02-23 | GSE172336 | GEO
Project description:We performed microarray analyses comparing perivascular adipose tissue gene expression of thoracic aortic vs. left internal mammary artery in human subjects with coronary artery disease. 300 genes were significantly upregulated in aortic fat, with at least 63 genes involved in inflammation and atherosclerosis. qPCR validation demonstrated increased expression of WNT-5A related genes, and CCL-2, CCL-8, JNK, and IL-6 gene expression.
2021-02-02 | GSE152326 | GEO
Project description:Glioblastoma stem cells (GSCs) have been reported to be found near the blood vessels. We wanted to identify the perivascular GSCs by combining the label retention approach with vascular perfusion. GSCs, like most of the stem cells, are in a quiescent state. Label retention approach involves staining the cells with a uniform membrane labeling dye (PKH26) and allowing them to grow in vivo in NOD SCID mice. Slow-dividing stem cells will retain the dye to a greater extent and perivascular cells are identified by injecting the mice with vascular perfusion dye (Hoechst 33342) 5 min prior to sacrifice. Perivascular GSCs (positive for Hoechst 33342 and pKH26 dye - dubbed as H+P+) were compared with the rest of the perivascular glioma cells (H+P-).
2022-01-01 | E-MTAB-9607 | biostudies-arrayexpress