Browse
Submit Data
Databases
API
Help

Dataset Information

29 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-Cell Transcriptomics Reveals Endothelial Plasticity During Diabetic Atherogenesis.

ABSTRACT: Atherosclerosis is the leading cause of cardiovascular diseases, which is also the primary cause of mortality among diabetic patients. Endothelial cell (EC) dysfunction is a critical early step in the development of atherosclerosis and aggravated in the presence of concurrent diabetes. Although the heterogeneity of the organ-specific ECs has been systematically analyzed at the single-cell level in healthy conditions, their transcriptomic changes in diabetic atherosclerosis remain largely unexplored. Here, we carried out a single-cell RNA sequencing (scRNA-seq) study using EC-enriched single cells from mouse heart and aorta after 12 weeks feeding of a standard chow or a diabetogenic high-fat diet with cholesterol. We identified eight EC clusters, three of which expressed mesenchymal markers, indicative of an endothelial-to-mesenchymal transition (EndMT). Analyses of the marker genes, pathways, and biological functions revealed that ECs are highly heterogeneous and plastic both in normal and atherosclerotic conditions. The metabolic transcriptomic analysis further confirmed that EndMT-derived fibroblast-like cells are prominent in atherosclerosis, with diminished fatty acid oxidation and enhanced biological functions, including regulation of extracellular-matrix organization and apoptosis. In summary, our data characterized the phenotypic and metabolic heterogeneity of ECs in diabetes-associated atherogenesis at the single-cell level and paves the way for a deeper understanding of endothelial cell biology and EC-related cardiovascular diseases.

SUBMITTER: Zhao G

PROVIDER: S-EPMC8170046 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Single-cell transcriptomics reveals receptor transformations during olfactory neurogenesis.

Project description:The sense of smell allows chemicals to be perceived as diverse scents. We used single-neuron RNA sequencing to explore the developmental mechanisms that shape this ability as nasal olfactory neurons mature in mice. Most mature neurons expressed only one of the ~1000 odorant receptor genes (Olfrs) available, and at a high level. However, many immature neurons expressed low levels of multiple Olfrs. Coexpressed Olfrs localized to overlapping zones of the nasal epithelium, suggesting regional biases, but not to single genomic loci. A single immature neuron could express Olfrs from up to seven different chromosomes. The mature state in which expression of Olfr genes is restricted to one per neuron emerges over a developmental progression that appears to be independent of neuronal activity involving sensory transduction molecules.

| S-EPMC5642900 | biostudies-literature

Single-cell transcriptomics reveals a mechanosensitive injury signaling pathway in early diabetic nephropathy.

Project description:BackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal disease, and histopathologic glomerular lesions are among the earliest structural alterations of DN. However, the signaling pathways that initiate these glomerular alterations are incompletely understood.MethodsTo delineate the cellular and molecular basis for DN initiation, we performed single-cell and bulk RNA sequencing of renal cells from type 2 diabetes mice (BTBR ob/ob) at the early stage of DN.ResultsAnalysis of differentially expressed genes revealed glucose-independent responses in glomerular cell types. The gene regulatory network upstream of glomerular cell programs suggested the activation of mechanosensitive transcriptional pathway MRTF-SRF predominantly taking place in mesangial cells. Importantly, activation of MRTF-SRF transcriptional pathway was also identified in DN glomeruli in independent patient cohort datasets. Furthermore, ex vivo kidney perfusion suggested that the regulation of MRTF-SRF is a common mechanism in response to glomerular hyperfiltration.ConclusionsOverall, our study presents a comprehensive single-cell transcriptomic landscape of early DN, highlighting mechanosensitive signaling pathways as novel targets of diabetic glomerulopathy.

| S-EPMC9830686 | biostudies-literature

Single-cell transcriptomics unveils gene regulatory network plasticity.

Project description:BackgroundSingle-cell RNA sequencing (scRNA-seq) plays a pivotal role in our understanding of cellular heterogeneity. Current analytical workflows are driven by categorizing principles that consider cells as individual entities and classify them into complex taxonomies.ResultsWe devise a conceptually different computational framework based on a holistic view, where single-cell datasets are used to infer global, large-scale regulatory networks. We develop correlation metrics that are specifically tailored to single-cell data, and then generate, validate, and interpret single-cell-derived regulatory networks from organs and perturbed systems, such as diabetes and Alzheimer's disease. Using tools from graph theory, we compute an unbiased quantification of a gene's biological relevance and accurately pinpoint key players in organ function and drivers of diseases.ConclusionsOur approach detects multiple latent regulatory changes that are invisible to single-cell workflows based on clustering or differential expression analysis, significantly broadening the biological insights that can be obtained with this leading technology.

| S-EPMC6547541 | biostudies-literature

Single-Cell Transcriptomics Reveals Zone-Specific Alterations of Liver Sinusoidal Endothelial Cells in Cirrhosis.

Project description:BackgroundDysfunction of liver sinusoidal endothelial cells (LSECs) is permissive for the progression of liver fibrosis and cirrhosis and responsible for its clinical complications. Here, we have mapped the spatial distribution of heterogeneous liver ECs in normal vs cirrhotic mouse livers and identified zone-specific transcriptomic changes of LSECs associated with liver cirrhosis using scRNA-seq technology.Approach & resultsCirrhosis was generated in endothelial specific green fluorescent protein (GFP) reporter mice through carbon tetrachloride inhalation for 12 weeks. GFP-positive liver EC populations were isolated from control and cirrhotic mice by FACS. We identified 6 clusters of liver EC populations including 3 clusters of LSECs, 2 clusters of vascular ECs and 1 cluster of lymphatic ECs. Based on previously reported LSEC-landmarks, we mapped the 3 clusters of LSECs in zones 1, 2, and 3, and determined phenotypic changes in each zone between control and cirrhotic mice. We found genes representing capillarization of LSECs (eg, CD34) as well as extracellular matrix genes were most upregulated in LSECs of zone 3 in cirrhotic mice, which may contribute to the development of basement membranes. LSECs in cirrhotic mice also demonstrated decreased expression of endocytic receptors, most remarkably in zone 3. Transcription factors (Klf2 [Kruppel-like factor-2], Klf4 [Kruppel-like factor-4], and AP-1) that induce nitric oxide production in response to shear stress were downregulated in LSECs of all zones in cirrhotic mice, implying increased intrahepatic vascular resistance.ConclusionThis study deepens our knowledge of the pathogenesis of liver cirrhosis at a spatial, cell-specific level, which is indispensable for the development of novel therapeutic strategies to target the most dysfunctional liver ECs.

| S-EPMC7903131 | biostudies-literature

Single cell sequencing reveals endothelial plasticity with transient mesenchymal activation after myocardial infarction.

Project description:Endothelial cells play a critical role in the adaptation of tissues to injury. Tissue ischemia induced by infarction leads to profound changes in endothelial cell functions and can induce transition to a mesenchymal state. Here we explore the kinetics and individual cellular responses of endothelial cells after myocardial infarction by using single cell RNA sequencing. This study demonstrates a time dependent switch in endothelial cell proliferation and inflammation associated with transient changes in metabolic gene signatures. Trajectory analysis reveals that the majority of endothelial cells 3 to 7 days after myocardial infarction acquire a transient state, characterized by mesenchymal gene expression, which returns to baseline 14 days after injury. Lineage tracing, using the Cdh5-CreERT2;mT/mG mice followed by single cell RNA sequencing, confirms the transient mesenchymal transition and reveals additional hypoxic and inflammatory signatures of endothelial cells during early and late states after injury. These data suggest that endothelial cells undergo a transient mes-enchymal activation concomitant with a metabolic adaptation within the first days after myocardial infarction but do not acquire a long-term mesenchymal fate. This mesenchymal activation may facilitate endothelial cell migration and clonal expansion to regenerate the vascular network.

| S-EPMC7846794 | biostudies-literature

Single-cell transcriptomics reveals distinct inflammation-induced microglia signatures

Project description:Microglia are specialized parenchymal-resident phagocytes of the central nervous system (CNS) that actively support, defend and modulate the neural environment. Dysfunctional microglia responses are thought to worsen CNS diseases, nevertheless their impact during neuroinflammatory processes remains largely obscure. Here, using a combination of single-cell RNA sequencing and multicolour flow cytometry, we comprehensively profile microglia in the brain of lipopolysaccharide (LPS)-injected mice. By excluding the contribution of other immune CNS-resident and peripheral cells, we show that microglia isolated from LPS-injected mice display a global downregulation of their homeostatic signature together with an upregulation of inflammatory genes. Notably, we identify distinct microglia activated profiles under inflammatory conditions, which greatly differ from neurodegenerative disease-associated profiles. These results provide insights into microglia heterogeneity and establish a resource for the identification of specific phenotypes in CNS disorders, such as neuroinflammatory and neurodegenerative diseases.

| S-SCDT-EMBOR-2018-46171-T | biostudies-other

Single nuclei transcriptomics reveals altered endothelial cell function, permeability, and cognition in diabetic mice.

Project description:Diabetes (DM) increases cardiovascular and cerebrovascular disease risk. However, the mechanism of DM-associated microvascular dysfunction and neuroinflammation remain unknown. We present a global assessment of endothelial cell-specific gene expression and integrated transcriptomics directly addressing hippocampal endothelium in diabetic mice, with the goal of determining the effect of DM in endothelial cell function and potential implications to vascular dementia. We observe for the first-time differential gene expression with strong signatures of cell signaling, activation of pathways for endothelial dysfunction, and neurodegeneration. Moreover, we identified that the integrated transcriptomic changes associate with blood brain barrier disruption by magnetic resonance imaging, and behavioral alterations, and correlate with the clinical gene profile of dementia patients, revealing opportunities for treatments with specificity for molecular pathology.

2024-01-22 | GSE241142 | GEO

Integrative Single-Cell Transcriptomics Reveals Molecular Networks Defining Neuronal Maturation During Postnatal Neurogenesis.

Project description:In mammalian hippocampus, new neurons are continuously produced from neural stem cells throughout life. This postnatal neurogenesis may contribute to information processing critical for cognition, adaptation, learning, and memory, and is implicated in numerous neurological disorders. During neurogenesis, the immature neuron stage defined by doublecortin (DCX) expression is the most sensitive to regulation by extrinsic factors. However, little is known about the dynamic biology within this critical interval that drives maturation and confers susceptibility to regulatory signals. This study aims to test the hypothesis that DCX-expressing immature neurons progress through developmental stages via activity of specific transcriptional networks. Using single-cell RNA-seq combined with a novel integrative bioinformatics approach, we discovered that individual immature neurons can be classified into distinct developmental subgroups based on characteristic gene expression profiles and subgroup-specific markers. Comparisons between immature and more mature subgroups revealed novel pathways involved in neuronal maturation. Genes enriched in less mature cells shared significant overlap with genes implicated in neurodegenerative diseases, while genes positively associated with neuronal maturation were enriched for autism-related gene sets. Our study thus discovers molecular signatures of individual immature neurons and unveils potential novel targets for therapeutic approaches to treat neurodevelopmental and neurological diseases.

| S-EPMC6361276 | biostudies-literature

Single-cell transcriptomics reveals activation of endothelial cell and identifies LHPP as a potential target in ulcerative colitis.

Project description:This study delves into Ulcerative colitis (UC), a persistent gastrointestinal disorder marked by inflammation and ulcers, significantly elevating colorectal cancer risk. The emergence of single-cell RNA sequencing (scRNA-seq) technology has opened new avenues for dissecting the intricate cellular dynamics and molecular mechanisms at play in UC pathology. By analyzing scRNA-seq data from individuals with UC, our study has revealed a consistent enhancement of inflammatory response pathways throughout the course of the disease, alongside detailing the characteristics of endothelial cell damage within colitis environments. A noteworthy finding is the downregulation of Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase (LHPP), which exhibited a inversely correlate with STAT3 expression levels. The markedly reduced expression of LHPP in both the tissues and plasma of UC patients positions LHPP as a compelling target for therapeutic intervention. Our findings highlight the pivotal role LHPP could play in moderating inflammation, spotlighting its potential as a crucial molecular target in the quest to understand and treat UC.

| S-EPMC11004881 | biostudies-literature

Single-cell transcriptomics reveals immune infiltrate in sepsis.

Project description:Immune cells and immune microenvironment play important in the evolution of sepsis. This study aimed to explore hub genes related to the abundance of immune cell infiltration in sepsis. The GEOquery package is used to download and organize data from the GEO database. A total of 61 differentially expressed genes (DEGs) between sepsis samples and normal samples were obtained through the 'limma' package. T cells, natural killer (NK) cells, monocytes, megakaryocytes, dendritic cells (DCs), and B cells formed six distinct clusters on the t-distributed stochastic neighbor embedding (t-SNE) plot generated using the Seurat R package. Gene set enrichment analysis (GSEA) enrichment analysis showed that sepsis samples and normal samples were related to Neutrophil Degranulation, Modulators of Tcr Signaling and T Cell Activation, IL 17 Pathway, T Cell Receptor Signaling Pathway, Ctl Pathway, Immunoregulatory Interactions Between a Lymphoid and A Non-Lymphoid Cell. GO analysis and KEGG analysis of immune-related genes showed that the intersection genes were mainly associated with Immune-related signaling pathways. Seven hub genes (CD28, CD3D, CD2, CD4, IL7R, LCK, and CD3E) were screened using Maximal Clique Centrality, Maximum neighborhood component, and Density of Maximum Neighborhood Component algorithms. The lower expression of the six hub genes (CD28, CD3D, CD4, IL7R, LCK, and CD3E) was observed in sepsis samples. We observed the significant difference of several immune cell between sepsis samples and control samples. Finally, we carried out in vivo animal experiments, including Western blotting, flow cytometry, Elisa, and qPCR assays to detect the concentration and the expression of several immune factors.

| S-EPMC10126435 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data