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Spatial and single-cell transcriptional profiling identifies functionally distinct human dermal fibroblast subpopulations

ABSTRACT: Spatial and single-cell transcriptional profiling identifies functionally distinct human dermal fibroblast subpopulations

PROVIDER: PRJNA412084 | ENA |

REPOSITORIES: ENA

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Spatial and single-cell transcriptional profiling identifies functionally distinct human dermal fibroblast subpopulations

Project description:Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining tissue integrity. We have previously shown that mouse skin connective tissue, the dermis, is comprised of functionally distinct fibroblast lineages. However, the extent of fibroblast heterogeneity in human skin is unknown. Here, using a combination of spatial transcriptional profiling of human and mouse dermis and single cell transcriptional profiling of human dermal fibroblasts, we show that there are at least four distinct fibroblast populations in adult human skin. We define markers permitting prospective isolation of these cells and show that although marker expression is rapidly lost in culture, different fibroblast subpopulations retain distinct functionality in terms of Wnt signalling, T cell communication and the ability to support human epidermal reconstitution in organotypic culture. Furthermore, while some fibroblast subpopulations are spatially segregated, others are not. These findings have profound implications for normal wound healing and diseases characterized by excessive fibrosis, and suggest that ex vivo expansion or in vivo ablation of specific fibroblast subpopulations may have therapeutic applications.

2018-02-12 | GSE109822 | GEO

Spatial and single-cell transcriptional profiling identifies functionally distinct human dermal fibroblast subpopulations

Project description:Spatial and single-cell transcriptional profiling identifies functionally distinct human dermal fibroblast subpopulations

| PRJNA432084 | ENA

Expression data from human dermal fibroblast subpopulations

Project description:Expression data from human dermal fibroblast subpopulations

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Expression data from human dermal fibroblast subpopulations

Project description:Fibroblasts are the main dermis-resident cells, yet they remain poorly characterized. Fundamentally, fibroblasts originate from the same population of mesenchymal cells but fibroblast subpopulations have been identified. Papillary and reticular fibroblasts were characterized based on their respective location in the papillary and reticular dermis. Here, we identified a new subset of fibroblasts, located in human papillary dermis and displaying specific features such as their organization into cell clusters. We used microarrays to detail the gene expression profiles of the novel fibroblast subpopulation we have identified compared to papillary and reticualr fibroblasts and notably the relative contribution of the different fibroblast subpopulations to the extracellular matrix of the dermis.

2019-04-01 | GSE104318 | GEO

Spatial and Single-Cell Transcriptional Profiling Identifies Functionally Distinct Human Dermal Fibroblast Subpopulations.

Project description:Previous studies have shown that mouse dermis is composed of functionally distinct fibroblast lineages. To explore the extent of fibroblast heterogeneity in human skin, we used a combination of comparative spatial transcriptional profiling of human and mouse dermis and single-cell transcriptional profiling of human dermal fibroblasts. We show that there are at least four distinct fibroblast populations in adult human skin, not all of which are spatially segregated. We define markers permitting their isolation and show that although marker expression is lost in culture, different fibroblast subpopulations retain distinct functionality in terms of Wnt signaling, responsiveness to IFN-γ, and ability to support human epidermal reconstitution when introduced into decellularized dermis. These findings suggest that ex vivo expansion or in vivo ablation of specific fibroblast subpopulations may have therapeutic applications in wound healing and diseases characterized by excessive fibrosis.

| S-EPMC5869055 | biostudies-literature

Sphingolipids Control Dermal Fibroblast Heterogeneity

Project description:Sphingolipids Control Dermal Fibroblast Heterogeneity

| PRJNA703935 | ENA

Human Dermal Fibroblast Subpopulations and Epithelial Mesenchymal Transition Signals in Hidradenitis Suppurativa Tunnels are Normalized by Spleen Tyrosine Kinase Antagonism in Vivo

Project description:Nanostring nCounter Human Fibrosis V2.0 Panel Hidradenitis Suppurativa is a chronic inflammatory disease of which the pathogenesis is incompletely understood. Dermal fibroblasts have been previously identified as a major source of inflammatory cytokines, however information pertaining to the characteristics of subpopulations of fibroblasts in HS remains unexplored. Using in silico-deconvolution of whole-tissue RNAseq, Nanostring gene expression panels and confirmatory immunohistochemistry we identified fibroblast subpopulations in HS tissue and their relationship to disease severity and lesion morphology. Gene signatures of SFRP2+ fibroblast subsets were increased in lesional tissue, with gene signatures of SFRP1+ fibroblast subsets decreased. SFRP2+ and CXCL12+ fibroblast numbers, measured by IHC, were increased in HS tissue, with greater numbers associated with epithelialized tunnels and Hurley Stage 3 disease. Pro-inflammatory CXCL12+ fibroblasts were also increased, with reductions in SFRP1+ fibroblasts compared to healthy controls. Evidence of Epithelial Mesenchymal Transition was seen via altered gene expression of SNAI2 and altered protein expression of ZEB1, TWIST1, Snail/Slug, E-Cadherin and N-Cadherin in HS lesional tissue. The greatest dysregulation of EMT associated proteins was seen in biopsies containing epithelialized tunnels. The use of the oral Spleen tyrosine Kinase inhibitor Fostamatinib significantly reduced expression of genes associated with chronic inflammation, fibroblast proliferation and migration suggesting a potential role for targeting fibroblast activity in HS.

2023-05-23 | GSE220454 | GEO

Spatial and single-cell transcriptional profiling identifies functionally distinct human dermal fibroblast subpopulations

Project description:Expression data from P2 mouse fibroblasts sorted for CD26, Sca1 and Dlk1. We have sorted mouse fibroblasts using the different lineages markers In this dataset, we include 3 biological replicates for CD26+, Sca1+Dlk1-, Sca1+Dlk1+ and Sca1-Dlk1+, a total of 12 samples

2018-02-12 | GSE104225 | GEO

Single-cell transcriptomes of the aging human skin reveal loss of fibroblast priming

Project description:Fibroblasts are the main dermal cell type and are essential for the architecture and function of human skin. Important differences have been described between fibroblasts localized in distinct dermal layers, and these cells are also known to perform varied functions. However, this phenomenon has not been analyzed comprehensively yet. Here we have used single-cell RNA sequencing to analyze >15,000 cells from a sun-protected area in young and old donors. Our results define four main fibroblast subpopulations that can be spatially localized and functionally distinguished. Importantly, intrinsic aging reduces this fibroblast ‘priming’, generates distinct expression patterns of skin aging-associated genes, and substantially reduces the interactions of dermal fibroblasts with other skin cell types. Our work thus provides comprehensive evidence for a functional specialization of human dermal fibroblasts and suggests that the age-related loss of fibroblast priming contributes to human skin aging.

2020-03-31 | GSE130973 | GEO

Sphingolipids Control Dermal Fibroblast Heterogeneity

Project description:Human cells produce thousands of lipids that impact biological processes in ways we are only starting to characterize. The cellular composition in lipids changes during differentiation and also varies across individual cells of the same type. Yet, whether and how cell-to-cell differences in lipid composition affect cell phenotypes remain unknown. Here we have measured the lipidomes and transcriptomes of individual human dermal fibroblasts by coupling high-resolution mass spectrometry imaging to single-cell transcriptomics. We find that the cell-to-cell variation of specific lipid metabolic pathways contributes to the establishment of cell states involved in the organization of skin architecture. In fact, sphingolipid composition defines fibroblast subpopulations and its metabolic rewiring drives cell state transitions. These data uncover a role for cell-to-cell lipid heterogeneity in the determination of cell states and reveal a new regulatory component to the self-organization of multicellular systems.

2021-02-23 | GSE167209 | GEO

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