Spatial localisation of human skin fibroblasts
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ABSTRACT:
PROVIDER: PRJEB95110 | ENA |
REPOSITORIES: ENA
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Project description:Our understanding of how human skin cells differ according to anatomical site and tumour formation is limited. To address this we have created a multi-scale spatial atlas of healthy skin and basal cell carcinoma (BCC), incorporating in vivo optical coherence tomography, single cell RNA sequencing, spatial global transcriptional profiling and in situ sequencing. Computational spatial deconvolution and projection revealed the localisation of distinct cell populations to specific tissue contexts. Although cell populations were conserved between healthy anatomical sites and in BCC, mesenchymal cell populations including fibroblasts and pericytes retained signatures of developmental origin. Spatial profiling and in silico lineage tracing support a hair follicle origin for BCC and demonstrate that cancer-associated fibroblasts are an expansion of a POSTN+ subpopulation associated with hair follicles in healthy skin. RGS5+ pericytes are also expanded in BCC suggesting a role in vascular remodelling. We propose that the identity of mesenchymal cell populations is regulated by signals emanating from adjacent structures and that these signals are repurposed to promote the expansion of skin cancer stroma. The resource we have created is publicly available in an interactive format for the research community.
2023-12-22 | E-MTAB-13085 | biostudies-arrayexpress
Project description:Our understanding of how human skin cells differ according to body site and tumour formation is limited. To address this we have created a multi-scale spatial atlas of healthy skin and basal cell carcinoma (BCC), incorporating in vivo optical coherence tomography, single cell RNA sequencing, spatial global transcriptional profiling and in situ sequencing. Computational spatial deconvolution and projection revealed the localisation of distinct cell populations to specific tissue contexts. Although cell populations were conserved between healthy anatomical sites and in BCC, mesenchymal cell populations including fibroblasts and pericytes retain signatures of developmental origin. Spatial profiling and in silico lineage tracing support a hair follicle origin for BCC and demonstrate that cancer-associated fibroblasts are an expansion of a POSTN+ subpopulation associated with hair follicles in healthy skin. RGS5+ pericytes are also expanded in BCC suggesting a role in vascular remodelling during cancer neovascularization. Our findings suggest that the identity of mesenchymal cell populations is regulated by signals emanating from adjacent structures and that these signals are repurposed to promote the expansion of skin cancer stroma. The resource we have created is publicly available in an interactive format for the research community.
2023-12-22 | E-MTAB-13084 | biostudies-arrayexpress
Project description:Spatial organization of different cell types within prenatal skin across various anatomical sites is not well understood. To address this, here we have generated spatial transcriptomics data from prenatal facial and abdominal skin obtained from a donor at 10 post conception weeks. This in combination with our prenatal skin scRNA-seq dataset has helped us map the location of various identified cell types.
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Project description:<p><strong>INTRODUCTION:</strong> A decline in mitochondrial function represents a key factor of a large number of inborn errors of metabolism, which lead to an extremely heterogeneous group of disorders.</p><p><strong>OBJECTIVES:</strong> To gain insight into the biochemical consequences of mitochondrial dysfunction, we performed a metabolic profiling study in human skin fibroblasts using galactose stress medium, which forces cells to rely on mitochondrial metabolism.</p><p><strong>METHODS:</strong> Fibroblasts from controls, complex I and pyruvate dehydrogenase (PDH) deficient patients were grown under glucose or galactose culture condition. We investigated extracellular flux using Seahorse XF24 cell analyzer and assessed metabolome fingerprints using NMR spectroscopy.</p><p><strong>RESULTS:</strong> Incubation of fibroblasts in galactose leads to an increase in oxygen consumption and decrease in extracellular acidification rate, confirming adaptation to a more aerobic metabolism. NMR allowed rapid profiling of 41 intracellular metabolites and revealed clear separation of mitochondrial defects from controls under galactose using partial least squares discriminant analysis. We found changes in classical markers of mitochondrial metabolic dysfunction, as well as unexpected markers of amino acid and choline metabolism. PDH deficient cell lines showed distinct upregulation of glutaminolytic metabolism and accumulation of branched-chain amino acids, while complex I deficient cell lines were characterized by increased levels in choline metabolites under galactose.</p><p><strong>CONCLUSION:</strong> Our results show the relevance of selective culture methods in discriminating normal from metabolic deficient cells. The study indicates that untargeted fingerprinting NMR profiles provide physiological insight on metabolic adaptations and can be used to distinguish cellular metabolic adaptations in PDH and complex I deficient fibroblasts.</p>
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Project description:Wound healing within the oral mucosa results in minimal scar formation compared to wounds within the skin. We have recently demonstrated distinct differences in the ageing profiles of cells (oral mucosal and patient-matched skin fibroblasts) isolated from these tissues. We hypothesize that the increased replicative potential of oral mucosal fibroblasts may confer upon them preferential wound healing capacities. Passage-matched early cultures of oral mucosal fibroblasts and skin fibroblasts demonstrated distinct gene expression profiles with a number of genes linked to wound healing/tissue repair. We analyzed the gene expression profiles of oral mucosal and patient-matched skin fibroblasts for multiple patients both prior to (0h) and (6h) following a wounding stimulus.
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Project description:RNA-seq analysis of NRF2 silenced human skin fibroblasts
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Project description:Connective tissue growthfactor (CTGF/CCN2) is a matricellular protein induced by transforming growth factor-beta (TGF-beta) and intimately involved with tissue repair and overexpressed in various fibrotic conditions. We have previously shown that keratinocytes in vitro downregulate TGF-beta induced expression of CTGF in fibroblasts by an interleukin-1 alfa (IL-1alfa) dependent mechanism. With this study we want to get a better overall perspective who fibroblasts respond on TGF-beta and in a TGF-Beta stinulated system, what effect addition of IL-1 alfa have. This to understand the expression of CTGF in human fibroblasts which in turn have implications for the pathogenesis of fibrotic conditions involving the skin. Microarray was performed on human skin fibroblast RNA from one patient, Fibroblasts were seeded in vitro as a control (Control, C), TGF-beta were added to fibroblasts and incubated for 16 h (addition of TGF-beta, T) and both IL-1alfa and TGF-beta were added to fibroblasts for 16 h (addition of IL-1alfa and TGF-beta, IT). Each condition (C,T and IT) were done in three replicates.
2016-04-14 | E-GEOD-69447 | biostudies-arrayexpress
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