Expression data from mouse skin fibroblasts in homeostasis, inflammation and cancer
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE156197 | GEO | 2021/02/08
REPOSITORIES: GEO
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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.
2011-01-01 | GSE21648 | GEO
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. Differences in the gene expression profiles of oral mucosal and patient-matched skin fibroblasts were anlazyed for multiple patients both prior to (0h) and (6h) following a wounding stimulus. Serum starvation and subsequent stimulation provides a model for wounding and RNA extracted at 0h and 6h following this stimulus was hybridized to Affymetrix microarrays for analysis. We sought to compare the expression profiles both between oral and normal fibroblasts, in both serum depleted and stimulated conditions and also compare differences between patients.
2011-01-01 | E-GEOD-21648 | biostudies-arrayexpress
Project description:Differentiation of fibroblasts to myofibroblasts is governed by the transforming growth factor beta (TGF-β) through a mechanism involving redox signaling and generation of reactive oxygen species (ROS). Myofibroblasts synthesize proteins of the extracellular matrix and display a contractile phenotype. Myofibroblasts are predominant contributors of wound healing and several pathological states, including fibrotic diseases and cancer. Inhibition of the ROS-generating enzyme NADPH oxidase 4 (NOX4) has been proposed to mitigate fibroblast to myofibroblast differentiation and to offer a therapeutic option for the treatment of fibrotic diseases. In this study, we addressed the role of NOX4 in physiological wound healing and in TGF-β-induced myofibroblast differentiation. We explored the phenotypic changes induced by TGF-β in primary skin fibroblasts isolated from Nox4-deficient mice by immunofluorescence, Western blotting and RNA sequencing. Mice deficient for Cyba, the gene coding for p22phox, a key subunit of NOX4 were used for confirmatory experiments as well as human primary skin fibroblasts. In vivo, the wound healing was similar in wild-type and Nox4-deficient mice. In vitro, despite a strong upregulation following TGF-β treatment, Nox4 did not influence skin myofibroblast differentiation. Nevertheless, up-regulation of the mitochondrial protein Ucp2 and the stress-response protein Hddc3, as well as down-regulation of Islr were observed in Nox4-deficient fibroblasts. Altogether, we provide extensive evidence challenging a profibrotic role of NOX4 in skin fibroblasts and show that Nox4 regulates Ucp2 and Hddc3 expression, suggesting the presence of a so far undescribed redox crosstalk between NOX4 and redox homeostasis in fibroblasts.
2023-03-15 | GSE197562 | GEO
Project description:Overexpression of activin A by keratinocytes accelerates excisional wound healing in mice. Activin-promoted wound healing is mediated via the stroma, specifically by the wound immune cells and fibroblasts. To determine if activin A alters the gene expression profile of wound fibroblasts, we performed RNA-sequencing of fibroblasts FACS-sorted from excisional skin wounds of activin overexpressing mice. We found that activin induces a pro-fibrotic gene expression profile of these fibroblasts, leading to the upregulation of genes involved in collagen biosynthesis and remodeling.
2020-04-14 | GSE134789 | GEO
Project description:Expression data from mouse skin fibroblasts in homeostasis, inflammation and cancer
| PRJNA657027 | ENA
Project description:Skin has distinct characteristics depending on the anatomical site; however, the cell and molecular differences, and their functional implications, have been little described. RNA-sequencing of healthy adult mouse skin from the abdomen, back, and face/cheek has revealed that dermis from different sites is distinct, and that this aligns with their diverse embryonic origins (abdominal dermis develops from lateral plate mesoderm, dorsal dermis from paraxial mesoderm, and cheek dermis from neural crest). The functional implications for wound repair are evident from the differences in extracellular matrix and cell migration observed in tissue and dermal fibroblasts from these sites, and the histological and transcriptional variations during a wound response.
2020-11-06 | GSE151850 | GEO
Project description:The skin is a protective barrier against external insults and any lesion must be rapidly and efficiently repaired. Dermal fibroblasts are the major source of extracellular connective tissue matrix and play an important role in wound healing. Vitamin C is an important water-soluble free radical scavenger and an essential cofactor for collagen synthesis by dermal fibroblasts and, consequently, may contribute to the maintenance of healthy skin. Using microarray analysis, we investigated the effects of long-term exposure to a stable vitamin C derivative, ascorbic acid 2-phosphate (AA2P), in contact-inhibited populations of primary human dermal fibroblasts. Compared with "scorbutic" cells, cells exposed to AA2P increased the expression of genes associated with DNA replication and repair and with the G(2)/M phase of the cell cycle. Consistent with the gene expression changes, AA2P increased the mitogenic stimulation of quiescent fibroblasts by serum factors and cell motility in the context of wound healing. Furthermore, AA2P-treated fibroblasts showed faster repair of oxidatively damaged DNA bases. We propose that vitamin C may protect the skin by promoting fibroblast proliferation, migration, and replication-associated base excision repair of potentially mutagenic DNA lesions, and we discuss the putative involvement of hypoxia-inducible transcription factor-1 and collagen receptor-related signaling pathways.
2009-02-10 | GSE11919 | GEO
Project description:The skin is a protective barrier against external insults and any lesion must be rapidly and efficiently repaired. Dermal fibroblasts are the major source of extracellular connective tissue matrix and play an important role in wound healing. Vitamin C is an important water-soluble free radical scavenger and an essential cofactor for collagen synthesis by dermal fibroblasts and, consequently, may contribute to the maintenance of healthy skin. Using microarray analysis, we investigated the effects of long-term exposure to a stable vitamin C derivative, ascorbic acid 2-phosphate (AA2P), in contact-inhibited populations of primary human dermal fibroblasts. Compared with scorbutic cells, cells exposed to AA2P increased the expression of genes associated with DNA replication and repair and with the G(2)/M phase of the cell cycle. Consistent with the gene expression changes, AA2P increased the mitogenic stimulation of quiescent fibroblasts by serum factors and cell motility in the context of wound healing. Furthermore, AA2P-treated fibroblasts showed faster repair of oxidatively damaged DNA bases. We propose that vitamin C may protect the skin by promoting fibroblast proliferation, migration, and replication-associated base excision repair of potentially mutagenic DNA lesions, and we discuss the putative involvement of hypoxia-inducible transcription factor-1 and collagen receptor-related signaling pathways. Experiment Overall Design: Gene expression changes in response to vitamin C were analysed by Microarray technology in GM5659 human skin fibroblasts. Cells were treated with 100 µM of AA or AA2P (or growth medium alone) added fresh every day for a period of 5 days before the vitamin C-induced gene expression changes were investigated. Control, AA- and AA2P-treated samples were collected from three independent experiments each.
2009-02-21 | E-GEOD-11919 | biostudies-arrayexpress
Project description:In adult mammals, skin wound healing has evolved to favor rapid repair through the formation of fibrotic scar. These dermal scars are dysfunctional and may lead to chronic disfigurement and disability, yet the biologic mechanisms that drive fibrosis and prevent tissue regeneration remain unknown. Here, we report that reindeer (Rangifer tarandus) antler velvet exhibits regenerative wound healing, whereas identical full-thickness injury in dorsal back skin of the same animal forms fibrotic scar. This regenerative capacity is retained even following ectopic transplantation of velvet to a scar-forming site, demonstrating that this latent regenerative capacity is innate to velvet cells and independent of local factors derived from the growing antler. Single cell RNA-sequencing of uninjured skin revealed a marked divergence in resting fibroblast transcriptional states and immunomodulatory function. Uninjured velvet fibroblast shared a striking resemblance with human fetal fibroblasts whereas uninjured back skin fibroblasts exhibited an overrepresentation of pro-inflammatory genes resembling adult human fibroblasts. Identical skin injury resulted in site-specific fibroblast polarization; back fibroblasts exacerbated the inflammatory response, whereas velvet fibroblasts adopted an immunosuppressive state and reverted back to a regeneration-competent ground state. Consequently, velvet wounds exhibited an accelerated adoption of anti-inflammatory immune states and an expedited resolution of immune response. This study demonstrates reindeer as a novel comparative mammalian model to study both adult skin regeneration (velvet) and scar formation (back skin) within the same animal. Our study underscores the importance of fibroblast heterogeneity in shaping local immune cell functions that ultimately polarize wound healing outcomes. Purposeful, acute modulation of fibroblast-mediated immune signaling represents an important therapeutic avenue to mitigate scar and improve wound healing.
2022-12-08 | GSE207021 | GEO
Project description:This study analyzes gene expression associated with papilloma development in Tg.AC v-Ha-ras transgenic mice and identifies novel genes and biological processes that may be critical to skin carcinogenesis in these mice. Epidermal abrasion was used to synchronously induce epidermal regeneration in FVB/N wild type and transgenic Tg.AC mice. Skin papillomagenesis was uniquely induced in Tg.AC mice, and gene expression profiling was carried out using a 22,000 element mouse DNA microarray. Histological analysis showed that papillomas developed at a high rate by day 30 after abrasion in transgenic animals, while no papilloma developed in wild type mice. Transgene specific differentially expressed genes were identified at day 30 post-abrasion and these genes were annotated using EASE software and literature mining. Annotated and non-annotated genes associated with papilloma development were identified and clustering analysis revealed groups of genes that are coordinately expressed. A number of genes associated with differentiation and development were also physically clustered on mouse chromosome 16, including 16B3 that contains several Stefins and stefin-like genes, and 16A1 containing a number of keratin associated protein genes. Additional analyses presented here yield novel insights into the genes and processes involved in papilloma development in Tg.AC mice. Keywords: Time course of papilloma tumorigenesis between genetically modified strains after skin abrasion.
2008-04-11 | GSE11136 | GEO