RNA-seq analysis of human primary keratinocytes and skin
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001002981 | EGA |
REPOSITORIES: EGA
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Project description:RNA sequencing analysis comparing epidermal subpopulations in normal and inflamed skin.
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Project description:Epidermal homeostasis is governed by a balance between keratinocyte proliferation and differentiation with contributions from cell-cell interactions, but conserved or divergent mechanisms governing this equilibrium across species, and how an imbalance contributes to skin disease, are largely undefined. To address these questions, human skin single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (ST) data were integrated and compared to mouse skin data. Human skin cell type annotation was improved by using matched ST data, highlighting the importance of spatial context in cell type identity, and ST refined cellular communication inference. In cross-species analyses, we identified a human spinous keratinocyte subpopulation that exhibited proliferative capacity and a heavy-metal processing signature, which was absent in mouse and may account for species differences in epidermal thickness. This human subpopulation was expanded in psoriasis and zinc-deficiency dermatitis, attesting to disease relevance and suggesting a paradigm of subpopulation dysfunction as a hallmark of disease. To assess additional potential subpopulation drivers of skin diseases, we performed cell-of-origin enrichment analysis within genodermatoses, nominating pathogenic cell subpopulations and their communication pathways, which highlighted multiple potential therapeutic targets. This integrated dataset is encompassed in a publicly available web resource to aid mechanistic and translational studies of normal and diseased skin.
2023-05-03 | GSE173651 | GEO
Project description:Environmental air pollution such as diesel smoke emission has been shown to have an adverse effect on human skin. Although epidemiological studies showing adverse effects such as oxidative stress-induced aging exists, studies showing the cellular and molecular response to such stress are rare. Using a primary skin keratinocyte model and TMT-based quantitative proteomics strategy, we studied the effects of chronic exposure to diesel particulate matter (DPE) and DPE vapor on the cellular proteome and the ability of a known anti-oxidant Vitamin E in ameliorating such changes. LC-MS3 analysis of DPE and/or its vapor exposed skin keratinocytes resulted in quantification of 4,490 proteins of which 201 and 374 proteins were significantly dysregulated (≥1.5 fold, p-value ≥0.05) in each condition, respectively. We observed distinct molecular alterations in chronic DPE and DPE vapor exposure models. Dysregulation of several cellular processes such as cell cycle and gene regulation, oxidative stress response proteins, skin barrier integrity and skin hydration were observed in both DPE and DPE vapor exposed cells.
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Project description:RNA-seq analysis of NRF2 silenced human skin fibroblasts
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Eligible study participants will be evaluated clinically for evidence of skin toxicity during their visits to the outpatient Oncology clinics. Study participants will undergo skin biopsies before sorafenib or regorafenib treatment is initiated and once rash develops or 12 weeks into treatment with sorafenib or regorafenib. Skin biopsies will be performed in Oncology clinics by the study investigators and clinic support staff.
Study participants will undergo both skin biopsies regardless of whether they develop a rash. In patients who develop a rash the most representative lesion will be biopsied. A normal appearing area of skin will be biopsied in participants who do not develop a rash.
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