Cb7eb312-831c-415e-b971-d86dcd643ecf - samples
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ABSTRACT:
PROVIDER: EGAD00001004980 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:RNA-sequencing techniques to profile the transcriptomes of lesional skin of diabetic patients
2020-10-07 | GSE154556 | GEO
Project description:The complex system by which the skin regulates immune responses to the external environment is unclear. Here, we investigated cell-cell interactions underlying cutaneous defense against S. aureus. Single-cell transcriptomics (scRNA-Seq) and unbiased network analysis revealed unexpected, dominant IL-17-mediated dermal reticular fibroblast-to-neutrophil communication. Multi-faceted in vitro omics studies demonstrated that IL-17 synergized with several factors including TNF⍺ to induce fibroblast NFKBIZ and chemokine secretion. Cultured fibroblasts drove robust neutrophil recruitment through NFKBIZ-dependent CXCR2 and CXCR4 ligands. Mice lacking IL-17R in fibroblasts (PdgfraΔIl17ra) were generated to determine the significance of fibroblast-neutrophil communication. PdgfraΔIl17ra mice exhibited drastically reduced skin neutrophilia in multiple disease models and reduced defense against S. aureus. These findings were translated to humans by comprehensive analysis of biopsies from psoriasis patients on and off anti-IL-17 treatment. Thus, dermal fibroblasts are critical for skin type 17 inflammation and represent a novel target for treatment of infection and inflammatory disease.
2024-02-15 | GSE230512 | GEO
Project description:The complex system by which the skin regulates immune responses to the external environment is unclear. Here, we investigated cell-cell interactions underlying cutaneous defense against S. aureus. Single-cell transcriptomics (scRNA-Seq) and unbiased network analysis revealed unexpected, dominant IL-17-mediated dermal reticular fibroblast-to-neutrophil communication. Multi-faceted in vitro omics studies demonstrated that IL-17 synergized with several factors including TNF⍺ to induce fibroblast NFKBIZ and chemokine secretion. Cultured fibroblasts drove robust neutrophil recruitment through NFKBIZ-dependent CXCR2 and CXCR4 ligands. Mice lacking IL-17R in fibroblasts (PdgfraΔIl17ra) were generated to determine the significance of fibroblast-neutrophil communication. PdgfraΔIl17ra mice exhibited drastically reduced skin neutrophilia in multiple disease models and reduced defense against S. aureus. These findings were translated to humans by comprehensive analysis of biopsies from psoriasis patients on and off anti-IL-17 treatment. Thus, dermal fibroblasts are critical for skin type 17 inflammation and represent a novel target for treatment of infection and inflammatory disease.
2024-02-14 | GSE230511 | GEO
Project description:single cell RNA-sequencing to profile the transcriptomes of lesional skin of diabetic patients at the cellular level.
2020-10-07 | GSE154557 | GEO
Project description:Clinical skin manifestations are common in diabetes; however, molecular mechanisms underlying such defects are largely unknown. Several findings indicate a role for microRNA (miRNA) in skin homeostasis. We investigated whether miRNA expression is altered in the skin of a Type 1 mouse model of diabetes. For this purpose, miRNA profiling by microarray analysis was performed on RNA extracted from the skin of diabetic mice and non-diabetic controls. >400 different miRNA species were identified, differential expression-analysis revealed miRNA dysregulation in diabetic skin. Interestingly, among the 30 most significantly modulated genes, 27 were downregulated and 3 were upregulated in diabetic mice. Pathway analysis using Tarbase showed an enrichment of signature-miRNA target genes in pathways with roles in skin homeostasis, such as TGF-β and Wnt.
2020-07-10 | GSE137605 | GEO
Project description:to gain a better understanding on the genomic mechanisms involved in defective healing in diabetes, we characterized here the gene expression profile and gene-gene interaction network of cultured fibroblasts derived from chronic diabetic leg ulcers comparatively to fibroblast obtained from control donors. Comparative transcriptomic analysis of cultured fibroblasts derived from six diabetic leg ulcers and five control fibroblasts using DNA microarrays and bioinformatics tools for studying gene-gene interaction networks.
2013-10-30 | E-GEOD-26365 | biostudies-arrayexpress
Project description:Netherton syndrome (NS) is a rare skin disease caused by loss-of-function mutations in the serine peptidase inhibitor Kazal type 5 (SPINK5) gene. Disease severity and the lack of efficacious treatments call for a better understanding of NS mechanisms. Here we describe a viable, Spink5 conditional knock-out (cKO) mouse model, allowing to study NS progression. Using comparative transcriptomics and proteomics, we determine a disease molecular profile conserved in mouse models and NS patients. Spink5 cKO mice and NS patients share skin barrier and inflammation signatures defined by up-regulation of proteases, IL-17, IL-36, IL-20 family cytokines. Furthermore, we show that systemic inflammation in Spink5 cKO mice is associated with thymic atrophy and is driven by innate immunity and IL-17/IL-22 signaling. By comparing skin transcriptomes and proteomes, we uncovered several putative substrates of tissue kallikrein-related proteases (KLKs), demonstrating that KLKs can proteolytically regulate IL-36 pro-inflammatory cytokines. Our study thus provides a conserved molecular framework for NS disease, adding new insights into its mechanisms and therapeutic targets.
2023-02-02 | MSV000091184 | MassIVE
Project description:Diabetes Mellitus (DM) is a chronic, severe disease rapidly increasing in incidence and prevalence and is associated with numerous complications. Patients with DM are at high risk of developing diabetic foot ulcers (DFU) that often lead to lower limb amputations, long term disability, and a shortened lifespan. Despite this, the effects of DM on human foot skin biology are largely unknown. Thus, the focus of this study was to determine whether DM changes foot skin biology predisposing it for healing impairment and development of DFU. Foot skin samples were collected from 20 patients receiving corrective foot surgery and, using a combination of multiple molecular and cellular approaches we performed comparative analyses of non-ulcerated non-neuropathic diabetic foot skin (DFS) and healthy non-diabetic foot skin (NFS). MicroRNA (miR) profiling of laser captured epidermis and primary dermal fibroblasts from both DFS and NFS samples identified 5 miRs de-regulated in the epidermis of DFS though none reached statistical significance. MiR-31-5p and miR-31-3p were most profoundly induced. Although none were significantly regulated in diabetic fibroblasts, miR-29c-3p showed a trend of up-regulation, which was confirmed by qPCR in a prospective set of 20 skin samples. Gene expression profiling of full thickness biopsies identified 36 de-regulated genes in DFS (>2 fold-change, unadjusted p-value ≤ 0.05). Of this group, three out of seven tested genes were confirmed by qPCR: SERPINB3 was up-regulated whereas OR2A4 and LGR5 were down-regulated in DFS. However no morphological differences in histology, collagen deposition, and number of blood vessels or lymphocytes were found. No difference in proliferative capacity was observed by quantification of Ki67 positive cells in epidermis. These findings suggest DM causes only subtle changes to foot skin. Since morphology, mRNA and miR levels were not affected in a major way, additional factors, such as neuropathy, vascular complications, or duration of DM, may further compromise tissue’s healing ability leading to development of DFUs. foot skin biopsies obtained from diabetic and non-diabetic people were thoroughly washed in DMEM supplemented with 2× Penicillin/Streptomycin/Fungizone, and gentamicin (50mg/L). After, the epidermis was removed from specimens, the dermis was finely minced and placed in 12-well plates. For the establishment of fibroblast cultures, DMEM (Life Technologies) supplemented with 10% FBS, HEPES (1.9mg/ml), streptomycin (100 μg/ml), penicillin (100 U/ml), and Fungizone Antimycotic (0.25 µg/mL) was used. RNA was isolated from cells (passage 1 or 2) using miRNeasy Mini Kit (QIAGEN). miR expression profiles of DFF and NFF fibroblasts were generated by nanoString nCounter miR Expression Assays (NanoString Technologies, Seattle, WA, USA) and analyzed using nSolver2.0 software following manufacturer's instructions. Data were normalized to gene controls included in the assays.
2015-05-01 | E-GEOD-68185 | biostudies-arrayexpress
Project description:Changes in the transcriptomes of human tissues with advancing age are poorly cataloged. Here, we set to identify the coding and long noncoding RNAs present in cultured primary skin fibroblasts collected from 82 healthy individuals across a wide age spectrum (22 to 89 years old) who participated in the GESTALT (Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing) study of the National Institute on Aging, NIH. Using high-throughput RNA sequencing and a linear regression model, we identified 1,437 coding RNA (mRNA) and 1,177 linear and circular long noncoding (lncRNA) that were differentially abundant as a function of age. GSEA analysis revealed select transcription factors implicated in coordinating the transcription of subsets of differentially abundant mRNAs, while LncSEA identified RNA-binding proteins predicted to contribute to the age-associated lncRNA profiles. In sum, we report age-associated changes in the global transcriptome, coding and noncoding, from healthy human skin fibroblasts, and propose that they might serve as biomarkers and therapeutic targets in aging skin.
2023-07-06 | GSE226189 | GEO
Project description:The role of PPARβ/δ in maintaining skin homeostasis during skin injury or inflammation has been widely studied. However, the majority of these reports based their studies in PPARβ/δ found in keratinocytes, which is the major cell type of the skin epidermis. The skin is mainy made up of the epidermis and dermis, and skin homeostasis is tightly regulated by complex crosstalks between epidermis and dermis. The dermis is predominantly made up of fibroblasts, and the predominant PPAR subtype in dermal fibroblasts is PPARβ/δ. Knowledge in the role of fibroblasts PPARβ/δ in skin homeostasis is lacking. To identify gene changes leading to phenotypical and biological functions alterations upon deletion of fibroblasts PPARβ/δ, we performed a comparative microarray gene expression analysis between Pparb/d^fl/fl and FSPCre-Pparb/d^fl/fl mice.
2018-04-03 | GSE71419 | GEO