Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-17539
PROVIDER: PRJNA118647 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The goal of the experiment: To characterize the dynamic gene expression profile of engineered human skin in vitro and after grafting, and compare with expression profile of uninjured human skin. Bioengineered skin substitutes can facilitate wound closure in massively burned patients, but deficiencies limit their outcomes compared to native skin autografts. To identify gene programs associated with their in vivo capabilities and limitations, we extended previous gene expression profile analyses to now compare engineered skin following in vivo grafting to both in vitro maturation and to normal human skin. Cultured skin substitutes were grafted to full-thickness wounds in athymic mice; biopsies for microarray analyses were collected at multiple in vitro and in vivo time points. Over 10,000 transcripts exhibited large-scale expression pattern differences during in vitro and in vivo maturation. Using hierarchical clustering, eleven different expression profile clusters were partitioned based on differential sample type and temporal stage-specific activation or repression. Analyses show that the wound environment exerts a massive influence on gene expression in skin substitutes. For example, in vivo healed skin substitutes gained expression of many native skin-expressed genes, including those associated with epidermal barrier and multiple categories of cell-cell and cell-basement membrane adhesion. In contrast, immunologic, trichogenic, and endothelial gene programs were largely lacking. These analyses suggest important areas to guide further improvement of engineered skin for both increased homology with native skin and enhanced wound healing. Experiment Overall Design: In the study, we hybridized RNA isolated from skin substitutes from days 3, 7, or 14 of in vitro incubation, and 3, 7, 14, 28, 42, or 56 days after transplantation to athymic mice, to Affymetrix Human U133 Plus 2.0 gene chips.
2009-09-07 | E-GEOD-17539 | biostudies-arrayexpress
Project description:The goal of the experiment: To characterize the dynamic gene expression profile of engineered human skin in vitro and after grafting, and compare with expression profile of uninjured human skin. Bioengineered skin substitutes can facilitate wound closure in massively burned patients, but deficiencies limit their outcomes compared to native skin autografts. To identify gene programs associated with their in vivo capabilities and limitations, we extended previous gene expression profile analyses to now compare engineered skin following in vivo grafting to both in vitro maturation and to normal human skin. Cultured skin substitutes were grafted to full-thickness wounds in athymic mice; biopsies for microarray analyses were collected at multiple in vitro and in vivo time points. Over 10,000 transcripts exhibited large-scale expression pattern differences during in vitro and in vivo maturation. Using hierarchical clustering, eleven different expression profile clusters were partitioned based on differential sample type and temporal stage-specific activation or repression. Analyses show that the wound environment exerts a massive influence on gene expression in skin substitutes. For example, in vivo healed skin substitutes gained expression of many native skin-expressed genes, including those associated with epidermal barrier and multiple categories of cell-cell and cell-basement membrane adhesion. In contrast, immunologic, trichogenic, and endothelial gene programs were largely lacking. These analyses suggest important areas to guide further improvement of engineered skin for both increased homology with native skin and enhanced wound healing.
2009-08-07 | GSE17539 | GEO
Project description:Transcription profiling by array of human grafted engineered skin substitutes
2015-09-04 | E-GEOD-17539 | ExpressionAtlas
Project description:Psoriasis is a chronic inflammatory disease of the skin for which no cure has emerged. Its complex etiology requires the development of an in vitro model that appropriately recapitulates the physiopathology of this disease. In this study, we exploited the self-assembly method in order to develop a new tissue-engineered model of psoriatic skin substitutes. To circumvent the addition of immune cells, we supplemented the reconstructed psoriatic substitutes with a cocktail of four cytokines, TNF-α, IL-1α, IL-6 and IL-17, and monitored their impact on global gene expression by DNA microarray. The cytokines-supplemented substitutes have a more irregular epidermis, with protuberances and much thinner areas. Most interestingly, gene profiling on microarrays identified several genes reported as being deregulated psoriasis skin in vivo. Indeed, expression of the S100A12, IL8, DEFB4A and KYNU genes increased dramatically compared to their level in normal skin substitutes (P <0.005 to <0.05). In addition, the ACSBG1 gene, reported to be repressed in psoriasis, was also repressed in the cytokines-supplemented psoriatic substitutes compared to the controls (P <0.005). The product encoded by the genes deregulated in the cytokines-supplemented substitutes belong to biological pathways, such as the inflammatory and the immune responses, that are similarly altered in psoriasis in vivo. In conclusion, addition of cytokines to involved psoriatic substitutes alters the transcriptome of these cells in a manner similar to that observed with psoriasis in vivo. The addition of this pro-inflammatory cocktail, comparable cytokine in vivo psoriasis, prepares us for the next step: the characterization of the model once added immune cells. Tissue-engineered psoriatic human skin (TEPHS) cultivated with (number of replicates: 3) or without (number of replicates: 3) Cytokines (IL-17a, IL-6, IL1a, TNF-a).
2015-04-11 | E-GEOD-67762 | biostudies-arrayexpress
Project description:Analysis of ex vivo isolated lymphatic endothelial cells from the dermis of patients to define type 2 diabetes-induced changes. Results preveal aberrant dermal lymphangiogenesis and provide insight into its role in the pathogenesis of persistent skin inflammation in type 2 diabetes. The ex vivo dLEC transcriptome reveals a dramatic influence of the T2D environment on multiple molecular and cellular processes, mirroring the phenotypic changes seen in T2D affected skin. The positively and negatively correlated dLEC transcripts directly cohere to prolonged inflammatory periods and reduced infectious resistance of patients´ skin. Further, lymphatic vessels might be involved in tissue remodeling processes during T2D induced skin alterations associated with impaired wound healing and altered dermal architecture. Hence, dermal lymphatic vessels might be directly associated with T2D disease promotion. Global gene expression profile of normal dermal lymphatic endothelial cells (ndLECs) compared to dermal lymphatic endothelial cells derived from type 2 diabetic patients (dLECs).Quadruplicate biological samples were analyzed from human lymphatic endothelial cells (4 x diabetic; 4 x non-diabetic). subsets: 1 disease state set (dLECs), 1 control set (ndLECs)
2012-06-01 | E-GEOD-38396 | biostudies-arrayexpress
Project description:Cultured skin substitutes, prepared using keratinocytes, fibroblasts and biopolymers, can facilitate closure of massive burn wounds by increasing the availability of autologous tissue for grafting. However, because they contain only two cell types, skin substitutes cannot replace all of the functions of native human skin. To better understand the physiological and molecular differences between cultured skin substitutes and native skin, we undertook a comprehensive analysis of gene expression in native skin, cultured keratinocytes, cultured fibroblasts, and skin substitutes using Affymetrix gene chip microarrays. Goals: Our analysis focused on identifying gene signatures that were highly characteristic of each cell and tissue type, and those that are regulated by the formation of cultured skin substitute from the individual components. Normalization: We used a normalization and referencing strategy that consisted of BioConductor/RMA Express RMA processing of the entire series of cel files followed by a per gene normalization in which the median value of expression for each gene was derived from the cultured samples only, and this was used as a reference for all samples including the cultured skin substitute. This approach allowed for the identification of genes that were higher and lower-expressed in the cultured skin relative to the individual cell types that were also expressed strongly or weakly in normal skin relative to the median value established by the three cell types. Results Summary:We identified six major clusters of coordinately regulated genes that were the most differentially expressed between groups. These clusters correspond to biomarker pools representing expression signatures for native skin, fibroblasts, keratinocytes, and cultured skin. The expression analysis revealed that entire clusters of genes were either up-regulated or down-regulated upon combination of fibroblasts and keratinocytes in cultured skin grafts. Further, several categories of genes were overexpressed in cultured skin substitutes compared with native skin, including genes associated with hyperproliferative skin or activated keratinocytes. The observed pattern of expression indicates that cultured skin substitutes in vitro, which display a well-differentiated epidermal layer, exhibit skin-like differentiation relative to gene expression patterns in the individual cells. This consists of both the activation of normal skin signature genes and the suppression of keratinocyte and fibroblast signatures. There is also a signature consistent with a hyperproliferative phenotype similar to wounded native skin. Experiment Overall Design: The sample series consists of native human skin (NHS) samples isolated from female donors undergoing reduction mammoplasty (breast skin) or abdominoplasty (abdomen skin). Skin samples from donors that were used to establish cultures of fibroblasts (CF) and keratinocytes (CK) were assigned donor numbers in the order they were processed in the laboratory, for example: 633, 634, etc. An additional human skin sample (C-1-Ref) was used only to make RNA as a standard control, and was therefore not assigned a donor number. Cultured skin substitutes (CSS) were prepared using isogenic CF and CK from each donor, and were cultured for 2 weeks in vitro to permit development of a stratified and cornified epidermal layer (confirmed by histology). For microarray analysis, RNA was isolated from intact NHS, from CF and CK in monolayer cultures, and from CSS. Samples are labeled indicating the sample type and donor number; for example, CF633 represents cultured fibroblasts from donor 633. To control for variation between individuals, four donors (= biological replicates) were used for each sample type: NHS, CF, CK, and CSS. Efforts were made to have complete sets of 4 samples from each donor, but intact RNA was not obtainable from 2 of the NHS samples (donors 634 and 651); these were replaced with NHS RNA from similar donors (donors C-1-Ref and 636). To check the fidelity of the microarray analysis, 2 of the RNA samples (CK639 and CSS651) were analyzed in duplicate (= technical replicates)
2007-09-06 | E-GEOD-3204 | biostudies-arrayexpress
Project description:Psoriasis is a chronic inflammatory disease of the skin for which no cure has emerged. Its complex etiology requires the development of an in vitro model that appropriately recapitulates the physiopathology of this disease. In this study, we exploited the self-assembly method in order to develop a new tissue-engineered model of psoriatic skin substitutes. To circumvent the addition of immune cells, we supplemented the reconstructed psoriatic substitutes with a cocktail of four cytokines, TNF-α, IL-1α, IL-6 and IL-17, and monitored their impact on global gene expression by DNA microarray. The cytokines-supplemented substitutes have a more irregular epidermis, with protuberances and much thinner areas. Most interestingly, gene profiling on microarrays identified several genes reported as being deregulated psoriasis skin in vivo. Indeed, expression of the S100A12, IL8, DEFB4A and KYNU genes increased dramatically compared to their level in normal skin substitutes (P <0.005 to <0.05). In addition, the ACSBG1 gene, reported to be repressed in psoriasis, was also repressed in the cytokines-supplemented psoriatic substitutes compared to the controls (P <0.005). The product encoded by the genes deregulated in the cytokines-supplemented substitutes belong to biological pathways, such as the inflammatory and the immune responses, that are similarly altered in psoriasis in vivo. In conclusion, addition of cytokines to involved psoriatic substitutes alters the transcriptome of these cells in a manner similar to that observed with psoriasis in vivo. The addition of this pro-inflammatory cocktail, comparable cytokine in vivo psoriasis, prepares us for the next step: the characterization of the model once added immune cells.
2015-04-11 | GSE67762 | GEO
Project description:Transcriptional profiling of Homo sapiens inflammatory skin diseases (whole skin biospies): Psoriasis (Pso), vs Atopic Dermatitis (AD) vs Lichen planus (Li), vs Contact Eczema (KE), vs Healthy control (KO) In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation. In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.
2014-12-02 | GSE63741 | GEO
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:Analysis of ex vivo isolated lymphatic endothelial cells from the dermis of patients to define type 2 diabetes-induced changes. Results preveal aberrant dermal lymphangiogenesis and provide insight into its role in the pathogenesis of persistent skin inflammation in type 2 diabetes. The ex vivo dLEC transcriptome reveals a dramatic influence of the T2D environment on multiple molecular and cellular processes, mirroring the phenotypic changes seen in T2D affected skin. The positively and negatively correlated dLEC transcripts directly cohere to prolonged inflammatory periods and reduced infectious resistance of patients´ skin. Further, lymphatic vessels might be involved in tissue remodeling processes during T2D induced skin alterations associated with impaired wound healing and altered dermal architecture. Hence, dermal lymphatic vessels might be directly associated with T2D disease promotion.
2012-06-02 | GSE38396 | GEO