Single cell ATACseq of control and AngII challenged mouse ascending aorta
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ABSTRACT:
PROVIDER: PRJNA883734 | ENA |
REPOSITORIES: ENA
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Project description:OBJECTIVE: When aortic cells are under stress, such as increased hemodynamic pressure, they adapt to the environment by modifying their functions, allowing the aorta to maintain its strength. To understand the regulation of this adaptive response, we examined the transcriptomic and epigenomic programs in aortic smooth muscle cells (SMCs) during the adaptive response to angiotensin II (AngII) infusion and determined its importance in protecting against aortic aneurysm and dissection. APPROACH AND RESULTS: In wild-type mice, AngII infusion increased medial thickness in the thoracic aorta. Single-cell RNA sequencing analysis revealed an adaptive response in thoracic SMCs characterized by the upregulation of genes with roles in wound healing, elastin and collagen production, proliferation, migration, cytoskeleton organization, cell-matrix focal adhesion, and AKT and TGF-β signaling. Further single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) analysis showed increased chromatin accessibility at the regulatory regions of adaptive genes and revealed the mechanical sensor YAP/TEADs as a top candidate transcription complex driving the increased abundance of these gene transcripts (e.g., Lox, Col5a2 and Tgfb2). In cultured human aortic SMCs, cyclic stretch activated YAP, which directly bound to the regulatory regions of the adaptive genes (e.g., Lox) and increased the abundance of their transcripts. Finally, SMC-specific Yap deletion in mice compromised this adaptive response in SMCs, leading to an increased incidence of aortic aneurysm and dissection and a trend of increased rupture. CONCLUSIONS: Aortic stress triggers the systemic epigenetic induction of adaptive response (e.g., wound healing, proliferation, and matrix organization) in thoracic aortic SMCs, that depends on functional biomechanical signal transduction (e.g., YAP signaling). Our study highlights the importance of the adaptive response in maintaining aortic homeostasis and preventing aortic disease development in mice.
2023-02-01 | GSE214082 | GEO
Project description:Here we undertook a proteomic investigation of ascending aorta from New Zealand White rabbits after 10 weeks on a high (2% w/w) cholesterol diet (HCD, n=5) or control diet (n=5) in order to profile the proteomic changes in response to the HCD. Histology confirmed intimal thickening in the HCD group and LC-MS/MS analysis of individually obtained ascending aorta extracts labelled with isobaric (iTRAQ) tags led to identification and quantitation of 453 unique proteins above the 1% false discovery rate threshold. Of 67 proteins showing significant differences in relative abundance (p<0.05), 62 were elevated and five decreased in ascending aorta from HCD-fed rabbits compared to controls. Six proteins were selected for validation using Multiple Reaction Monitoring which confirmed the iTRAQ results.
2018-06-21 | PXD002345 | Pride
Project description:ChIP-seq on human ascending aorta For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2017-10-25 | GSE106065 | GEO
Project description:CTCF ChIP-seq on human ascending aorta For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2017-10-24 | GSE105925 | GEO
Project description:Genome wide DNA methylation profiling of ascending aorta tissue samples from normal, aortic dissection and bicuspid aortic valve patients with aortic dilation. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across more than 450,000 CpGs in ascending aorta samples. Samples included 6 normal donors, 12 patients with aortic dissection and 6 patients with bicuspid aortic valve and dilated aorta.
2019-07-11 | GSE84274 | GEO
Project description:Bicuspid aortic valve is well known as a risk factor of dilation of ascending aorta. But the mechanisms of dialation are unknown. Morever, patients with bicuspid aortic valve tend to be aortic valve disease at younger age. After aortic valve surgery, if ascending aorta is dilated, the patient must be performed re-operation. For that reason, surgery for aortic root or ascending aorta is recommended to patient with bicuspid aortic valve with dilated ascending aorta. We thought that abnormality of cell cycle of the structure protein participated in ascending aorta dilation of patient with bicuspid aortic valve. We resected the wall of the ascending aota from patient undergoing aortic valve replacement for aortic valve stenosis during operation, and performed immunohistochemical staining for akt. Anti Akt antibodys were stained much on aortic media with bicuspoed aortic valve. Akt is a protein that is involved in mTOR / PI3K, and modulate the cell differenciation and proliferation. Further, the same samples were analyzed using a microarray method. On bicuspid aortic valve patients, the expression of TSC2 is reduced, and GβL is increased. TSC2 inhibit this pathway, and MLST8 activate this pathway. In the ascending aorta of BAV patients, PI3K / mTOR system is considered to be activated. When this pathway is activated, cell proliferation and cytodifferentiation are promoted abnormally,
2017-06-30 | GSE83675 | GEO
Project description:MERSCOPE profiling of non-aneurysmal and aneurysmal human ascending aorta
| PRJNA1010377 | ENA
Project description:Differentially expressed genes were identified by comparing the gene expression profiling of dissected ascending aorta with that of control. Results provide important information to indicate pathogenesis of aortic dissection.
2014-12-31 | GSE52093 | GEO
Project description:Objective - Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic extracellular matrix (ECM). The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family has recently been implicated in TAA formation. This study aimed to investigate the contribution of ADAMTS-5 to TAA development. Approach and Results - A model of aortic dilatation by angiotensin II (AngII) infusion was adopted in mice lacking the catalytic domain of ADAMTS-5 (Adamts5Δcat). Adamts5Δcat mice showed an attenuated rise in blood pressure whilst displaying increased dilatation of the ascending aorta. Interestingly, a comparison of the aortic ECM from AngII-treated wildtype and Adamts5Δcat mice revealed versican as the most up-regulated ECM protein in Adamts5Δcat mice. This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of low-density lipoprotein-related protein 1 (LRP1). Silencing LRP1 expression in human aortic smooth muscle cells reduced the expression of ADAMTS5, attenuated the generation of versikine but increased soluble ADAMTS-1. A similar increase in ADAMTS-1 was observed in aortas of AngII-treated Adamts5Δcat mice, but was not sufficient to maintain versican processing and prevent aortic dilatation. Conclusions - Our results support the emerging role of ADAMTS proteases in TAA. ADAMTS-5 rather than ADAMTS-1 is the key protease for versican regulation in murine aortas. Further studies are needed to define the ECM substrates of the different ADAMTS proteases and their contribution to TAA formation.
2018-05-08 | PXD009410 | Pride
Project description:Genome wide DNA methylation profiling of normal and ascending aorta tissue samples from normal and aortic dissection patients. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 485,512 CpGs in ascending aorta tissue samples. Samples included 4 normal donors and 4 patients with aortic dissection.
2022-11-02 | GSE202047 | GEO