Single-cell multimodal profiling of atherosclerosis identifies CD200 as a cell surface lineage marker of vascular smooth muscle cells and their derived cells
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PROVIDER: PRJNA1034596 | ENA |
REPOSITORIES: ENA
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Project description:Vascular smooth muscle cells (VSMCs) play a central role in the development of atherosclerosis due in part to their capability to phenotypically transition into either a protective or harmful state. However, the ability to identify and trace VSMCs and their progeny in vivo is limited due to the lack of well-defined VSMC cell surface markers. Therefore, investigations into VSMC fate must utilize lineage-tracing mouse models, which are time-consuming and challenging to generate and not feasible in humans. Here, we employed CITE-seq to characterize the phenotypic expression of 119 cell surface proteins in mouse atherosclerosis. We found that CD200 is a highly expressed and specific marker of VSMCs, which persists even with phenotypic modulation. We validated our findings using a combination of flow cytometry, qPCR, and immunohistochemistry, all confirming that CD200 can identify and mark VSMCs and their derived cells in early to advanced mouse atherosclerotic lesions. Additionally, we describe a similar expression pattern of CD200 in human coronary and carotid atherosclerosis. Thus, our data support the use of CD200 as a lineage marker for VSMCs and VSMC-derived cells in mouse and human atherosclerosis.
2024-04-12 | GSE246779 | 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 | GSE253903 | 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:High-Dimensional Single-Cell Multimodal Landscape of Human Carotid Atherosclerosis
| PRJNA1067637 | ENA
Project description:Mouse back skin was disassociated to single cells, sorted by cell surface markers and tested by microarrray To compare the gene expression of mouse bulge (CD34+CD200+CD49+) versus secondary hair germ (CD34-CD200+CD49+) versus interfollicular epidermis (CD34-CD200-CD49+) xx Bald scalp retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells Androgenetic alopecia (AGA) or common baldness results from a marked decrease in hair follicle size. This miniaturization may be related to loss of hair follicle stem or progenitor cells. To test this hypothesis, we analyzed bald and non-bald scalp from the same individuals for the presence of hair follicle stem and progenitor cells using flow cytometry to quantitate cells expressing CYTOKERATIN 15 (KRT15), CD200, CD34 and ALPHA-6-INTEGRIN (ITGA6). High levels of KRT15 expression correlated with stem cell properties of small cell size and quiescence. Cells with the highest level of KRT15 expression were maintained in bald scalp; however, distinct populations of CD200high ITGA6high cells and CD34-positive cells were markedly diminished. Consistent with a progenitor cell phenotype, the diminished populations localized closely to the stem-cell rich bulge area but were larger and more proliferative than the bulge stem cells. In functional assays, analogous CD200 high /Itga6 high cells from murine hair follicles were multipotent and generated new hair follicles in skin reconstitution assays. These findings suggest that a defect in stem cell activation plays a role in the pathogenesis of AGA. 4 independent biologic replicates (each pooled from 3 distinct mice) were sorted for Mouse bulge (CD34+CD200+CD49+) versus secondary hair germ (CD34-CD200+CD49+) versus interfollicular epidermis (CD34-CD200-CD49+)
2011-01-12 | E-GEOD-21568 | biostudies-arrayexpress
Project description:Purpose: Understanding immunosuppression in AML is critical . The goals of this study are to compare the transcriptomics of human CD3+ T cells from humanized mice exposed to CD200+/- AML. Methods: NSG mice were humanized with 10x10^6 healthy PBMCs prior to the introduction of CD200+ or CD200- OCI-AML3 cells. After 10 days, CD3+ T cells were isolated and RNA was sequenced. Results: T cells from mice with CD200+ AML were characterized by an enrichment of T cell activation pathways and a downregulation of numerous metabolic pathways, including OXPHOS and glycolysis. Conclusions: Our results demonstrate, for the first time, that CD200+ AML can directly impair T cell metbolism.
2021-04-24 | GSE173194 | GEO
Project description:Human hair follicles from normal areas of the scalp were disassociated to single cells, sorted and tested by microarrray To compare the expression of human CD200+ CD49+ hair follicle keratinocytes versus CD200-CD49+ keratinocytes
2011-01-12 | GSE21567 | GEO
Project description:High-Dimensional Single-Cell Multimodal Landscape of Human Carotid Atherosclerosis [CITE-seq]
| PRJNA1067645 | ENA
Project description:High-Dimensional Single-Cell Multimodal Landscape of Human Carotid Atherosclerosis [scRNA-seq]
| PRJNA1067646 | ENA
Project description:Mouse back skin was disassociated to single cells, sorted by cell surface markers and tested by microarrray To compare the gene expression of mouse bulge (CD34+CD200+CD49+) versus secondary hair germ (CD34-CD200+CD49+) versus interfollicular epidermis (CD34-CD200-CD49+) xx Bald scalp retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells Androgenetic alopecia (AGA) or common baldness results from a marked decrease in hair follicle size. This miniaturization may be related to loss of hair follicle stem or progenitor cells. To test this hypothesis, we analyzed bald and non-bald scalp from the same individuals for the presence of hair follicle stem and progenitor cells using flow cytometry to quantitate cells expressing CYTOKERATIN 15 (KRT15), CD200, CD34 and ALPHA-6-INTEGRIN (ITGA6). High levels of KRT15 expression correlated with stem cell properties of small cell size and quiescence. Cells with the highest level of KRT15 expression were maintained in bald scalp; however, distinct populations of CD200high ITGA6high cells and CD34-positive cells were markedly diminished. Consistent with a progenitor cell phenotype, the diminished populations localized closely to the stem-cell rich bulge area but were larger and more proliferative than the bulge stem cells. In functional assays, analogous CD200 high /Itga6 high cells from murine hair follicles were multipotent and generated new hair follicles in skin reconstitution assays. These findings suggest that a defect in stem cell activation plays a role in the pathogenesis of AGA.
2011-01-12 | GSE21568 | GEO