Integrated multi-omic high-throughput strategies across-species identified potential key diagnostic, prognostic, and therapeutic targets for atherosclerosis under high glucose conditions
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ABSTRACT:
PROVIDER: PRJNA1121910 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29338352_1.fastq.gz | Fastqsanger.gz | |||
| SRR29338352_2.fastq.gz | Fastqsanger.gz | |||
| SRR29338353_1.fastq.gz | Fastqsanger.gz | |||
| SRR29338353_2.fastq.gz | Fastqsanger.gz | |||
| SRR29338354_1.fastq.gz | Fastqsanger.gz |
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2024-12-16 | GSE269426 | GEO
Project description:Atherosclerotic plaques are complex tissues composed of a heterogeneous mixture of cells. However, our understanding of the comprehensive transcriptional and phenotypical landscape of the cells within these lesions is limited. To characterize the landscape of human carotid atherosclerosis in greater detail, we combined cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell RNA sequencing (scRNA-seq) to classify all cell types within lesions (n=21; 13 symptomatic) to achieve a comprehensive multimodal understanding of the cellular identities of atherosclerosis and their association with clinical pathophysiology. We identified 25 cell populations, each with a unique multi-omic signature, including macrophages, T cells, NK cells, mast cells, B cells, plasma cells, neutrophils, dendritic cells, endothelial cells, fibroblasts, and smooth muscle cells (SMCs). Among the macrophages, we identified 2 proinflammatory subsets enriched in IL1B or C1Q expression, 2 TREM2 positive foam cells (one expressing inflammatory genes), and subpopulations with a proliferative gene signature and SMC-specific gene signature with fibrotic pathways upregulated. Further characterization revealed various subsets of SMCs and fibroblasts, including SMC-derived foam cells. These foamy SMCs were localized in the deep intima of coronary atherosclerotic lesions. Utilizing CITE-seq data, we developed a flow cytometry panel, using cell surface proteins CD29, CD142, and CD90, to isolate SMC-derived cells from lesions. Lastly, we observed reduced proportions of efferocytotic macrophages, classically activated endothelial cells, and contractile and modulated SMC-derived cells, while inflammatory SMCs were enriched in plaques of clinically symptomatic vs asymptomatic patients. Our multimodal atlas of cell populations within atherosclerosis provides novel insights into the diversity, phenotype, location, isolation, and clinical relevance of the unique cellular composition of human carotid atherosclerosis. These findings facilitate both the mapping of cardiovascular disease susceptibility loci to specific cell types as well as the identification of novel molecular and cellular therapeutic targets for the treatment of the disease.
2024-04-12 | GSE253902 | GEO
Project description:Atherosclerotic plaques are complex tissues composed of a heterogeneous mixture of cells. However, our understanding of the comprehensive transcriptional and phenotypical landscape of the cells within these lesions is limited. To characterize the landscape of human carotid atherosclerosis in greater detail, we combined cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell RNA sequencing (scRNA-seq) to classify all cell types within lesions (n=21; 13 symptomatic) to achieve a comprehensive multimodal understanding of the cellular identities of atherosclerosis and their association with clinical pathophysiology. We identified 25 cell populations, each with a unique multi-omic signature, including macrophages, T cells, NK cells, mast cells, B cells, plasma cells, neutrophils, dendritic cells, endothelial cells, fibroblasts, and smooth muscle cells (SMCs). Among the macrophages, we identified 2 proinflammatory subsets enriched in IL1B or C1Q expression, 2 TREM2 positive foam cells (one expressing inflammatory genes), and subpopulations with a proliferative gene signature and SMC-specific gene signature with fibrotic pathways upregulated. Further characterization revealed various subsets of SMCs and fibroblasts, including SMC-derived foam cells. These foamy SMCs were localized in the deep intima of coronary atherosclerotic lesions. Utilizing CITE-seq data, we developed a flow cytometry panel, using cell surface proteins CD29, CD142, and CD90, to isolate SMC-derived cells from lesions. Lastly, we observed reduced proportions of efferocytotic macrophages, classically activated endothelial cells, and contractile and modulated SMC-derived cells, while inflammatory SMCs were enriched in plaques of clinically symptomatic vs asymptomatic patients. Our multimodal atlas of cell populations within atherosclerosis provides novel insights into the diversity, phenotype, location, isolation, and clinical relevance of the unique cellular composition of human carotid atherosclerosis. These findings facilitate both the mapping of cardiovascular disease susceptibility loci to specific cell types as well as the identification of novel molecular and cellular therapeutic targets for the treatment of the disease.
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Project description:High-Dimensional Single-Cell Multimodal Landscape of Human Carotid Atherosclerosis
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Project description:Purpose: This study aimed to explore the differential expression profiles of exosomal lncRNAs and evaluated their potential utility in the accurate diagnosis of LAA stroke. Methods: LncRNA profiles of exosomes in large artery atherosclerosis stroke and controls were generated by high-throughput sequencing. The sequence reads that passed quality filters were analyzed at the transcript isoform level with Hisat2, Trapnell, STAR. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Results: A total of 1020 differentially expressed lncRNAs were identified in LAA stroke patients. GO and KEGG pathway analyses indicated that their target genes are involved in atherosclerosis-related pathways, including inflammation, cell adhesion, and cell migration. 8 exosomal lncRNAs were confirmed with qRT–PCR.The result showed that the expression trend of differential expressed lncRNAs in validation was consistent with RNA-seq.Conclusion: Our study showed the differential expression of lncRNAs in plasma exosomes and presented related diagnostic potential for LAA stroke for the first time. The results suggested that exosomal lncRNA could be potential diagnostic tools in LAA stroke. Circular RNAs (circRNAs), novel endogenous noncoding RNAs, play diverse roles in ischemic stroke. Recently, the abundance and stability of circRNAs in exosomes have been identified. However, a comprehensive analysis of exosomal circRNAs in large artery atherosclerotic (LAA) stroke has not yet been reported. We performed RNA sequencing (RNA-Seq) to comprehensively identify differentially expressed exosomal circRNAs in five paired LAA and normal controls. RNA-Seq identified a total of 462 circRNAs in peripheral exosomes; there were 25 differentially expressed circRNAs among them. Additionally, circRNA competing endogenous RNA (ceRNA) network and translatable analysis revealed the potential functions of the exosomal circRNAs in LAA progression. Two ceRNA pathways involving 5 circRNAs, 2 miRNAs, and 3 mRNAs were confirmed by qRT-PCR. In the validation cohort, receiver operating characteristic (ROC) curve analysis identified two circRNAs as possible novel biomarkers, and a logistic model combining two and four circRNAs increased the area under the curve compared with the individual circRNAs.
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Project description:Cancer results from processes prone to selective pressure and dysregulation acting along the sequence-to-phenotype continuum DNA→RNA→Protein→Disease. However, the extent to which cancer is a manifestation of the proteome is unknown. Here we present an integrated omic map representing non-small cell lung carcinoma. Dysregulated proteins not previously implicated as cancer drivers are encoded throughout the genome including but not limited to regions of recurrent DNA amplification/deletion. Clustering reveals signatures composed of metabolism proteins particularly highly recapitulated between patient-matched primary and xenograft tumours. Interrogation of The Cancer Genome Atlas reveals cohorts of patients with lung and other cancers that have DNA alterations in genes encoding the signatures, and this was accompanied by differences in survival. The recognition of genome and proteome alterations as related products of selective pressure driving the disease phenotype may be a general approach to uncover and group together cryptic, polygenic disease drivers. Total RNAs from xenografts, primary tumor, and normal adjacent tissues were amplified by DASL kit and hybridized to Illumina HT12v4 chip
2014-10-09 | E-GEOD-62113 | biostudies-arrayexpress
Project description:We used transcriptomics to identify vascular gene expression profiles of high-fat-fed Tibetan minipig induced-hypercholesterolemia and atherosclerotic models, to verify the hypothesis that hypercholesterolemia induces innate and adaptive immune responses to accelerate atherosclerosis. Results showed that hypercholesterolemia and atherosclerosis models occurred in the high-fat fed minipigs at 8 and 24 weeks. GSEA analysis showed that the changes of hypercholesterolemia accelerated atherosclerosis were focused on immunity inflammation and lipid metabolism, immune cells such as NK cells and T cells participated in the biological processes. 4 significant modules of 344 overlapping DEGs were identified by STEM analysis. 6 hub genes (ITGB2, TYROBP, LCP2, PTPRC, C5AR1, and PTPN6) and two immune-related pathways (Natural killer cell-mediated cytotoxicity and T cell receptor signaling pathway) were identified by CytoHubba plugin and KEGG analysis. Correlation analysis showed that hub genes were significantly correlated with lipid deposition, IMT, WBC, CD4, and CD8, which was consistent with RT-PCR validation results. From above, this study reveals that hypercholesterolemia accelerate atherosclerosis progression by inducing innate and adaptive immune responses.
2020-03-30 | GSE140412 | GEO
Project description:Systemic immune responses induced by chronic hypercholesterolemia contribute to the initiation, progression and complications of atherosclerosis. However, it is common for individuals to change dietary habits over time. The consequences of an alternating high fat diet and the associated variations in plasma cholesterol levels on atherosclerosis are unknown. To address this relevant issue, we developed a novel protocol in atherosclerosis-prone mice that allowed us to compare the effects of alternate versus continuous high fat diet (HFD) on atherosclerosis, while keeping the overall period of exposure to HFD similar between groups. We showed that an alternate HFD lead to accelerated atherosclerosis in Ldlr-/- and Apoe 55 -/- mice compared to continuous HFD. This pro-atherogenic effect of alternate HFD was also observed in Apoe-/-Rag2 57 -/- mice lacking T, B, and NKT cells, ruling out the role of the adaptive immune system in the observed phenotype. Employing various complementary in vivo approaches, we discovered that discontinuing HFD in the alternate group downregulated Runx1, a negative regulator of inflammatory signaling pathways in the myeloid lineage. Consequently, after re61 exposure to HFD, myeloid progenitors were primed to respond to HFD re-exposure by differentiating into IL-1-producing immature neutrophils, and inducing a state of emergency myelopoiesis. Subsequently, neutrophils markedly increased in the peripheral blood, infiltrated atherosclerotic lesions and locally released neutrophil extracellular traps. Anti-Ly6G neutrophil depletion abolished the pro-atherogenic effects of alternate HFD. Specific deletion of Il1b and Il1 receptor confirmed that the IL-1 signaling pathway was a major driver of the pro67 inflammatory and pro-atherogenic neutrophil signature. Finally, treatment with anti-IL-1 neutralizing antibody or an inflammasome inhibitor during re-exposure to HFD reversed the pro-atherogenic effects of alternate HFD. In summary, we showed that alternate HFD accelerates atherosclerosis through IL-1-dependent neutrophil progenitor reprogramming.
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