Human skin metagenome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA293586 | ENA |
REPOSITORIES: ENA
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Project description:Autologous skin grafting is a standard treatment for skin defects such as burns. No artificial skin substitutes are functionally equivalent to autologous skin grafts. The cultured epidermis lacks the dermis and does not engraft deep wounds. Although reconstituted skin, which consists of cultured epidermal cells on a synthetic dermal substitute, can engraft deep wounds, it requires the wound bed to be well-vascularized and lacks skin appendages. In this study, we successfully generate complete skin grafts with PSC-derived epidermis with appendages on p63 knockout embryos' dermis. Donor PSC-derived keratinocytes encroach the embryos' dermis by eliminating p63 knockout keratinocytes based on cell-extracellular matrix adhesion mediated cell competition. Although the chimeric skin contains allogenic dermis, it is engraftable as long as autologous grafts. Furthermore, we could generate semi-humanized skin segments by human keratinocytes injection into the amnionic cavity of p63 knockout mice embryos. Niche encroachment opens the possibility of human skin graft production in livestock animals.
2024-02-10 | GSE252023 | GEO
Project description:The repair of skin and soft tissue defects has been a long-standing topic of interest in plastic surgery. Skin grafts and flaps are the most commonly used methods for such repair, but both have some disadvantages. If a high-quality skin flap transplantation outcome could be obtained through simple skin grafting, it would surely benefit a majority of patients. Transplantation of adipose-derived stem cells (ADSCs) into skin and soft tissue wounds is a promising “therapeutic angiogenesis” strategy in this context. In the present study, we used TNF-α to mobilize ADSCs for the tissue regenerative process. Then, we injected the TNF-α-activated ADSCs intradermally into the donor skin of full-thickness skin grafts (FTSGs). TNF-α may activate ADSCs through the TNF-α/NF-κB pathway and enhance the ability of ADSCs to signal the paracrine secretion of the angiogenic factor IL-8, ultimately promoting the angiogenesis of donor skin. The use of vasculature-rich donor skin for grafting presented in our study could accelerate skin graft anastomosis; shorten the nutrient deprivation time of the epidermis, hair follicles, and dermis; and thereby improve the survival of FTSGs. Overall, the findings of the present study demonstrate a possible mechanism through which TNF-α acts on ADSCs to improve their angiogenic capacity and provide a novel approach for the repair of skin and soft tissue wounds.
2023-02-27 | GSE226232 | GEO
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:The study was designed to determine the differential gene expression between burn eschar- and normal skin-derived pericytes. A comparison was also made to determine the gene expression between normal skin pericytes and normal skin fibroblasts and (2) comparison of differential gene expression between burn eschar pericytes and normal normal skin fibroblasts
2020-03-02 | GSE140926 | GEO
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. Keywords: Cell interaction and co-culture response expression profile
2005-08-29 | GSE3204 | GEO
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:Localized scleroderma (LoS), or morphea, refers to a group of rare autoimmune connective tissue diseases. Autologous fat grafting was able to correct volume loss in patients with LoS to improve facial disfigurement.However, whether it could exert a positive effect on reversing skin sclerosis remains unclear.
2023-11-20 | GSE247804 | GEO
Project description:Investigation into murine dermal burn wound. Mouse thermal injury induced, and skin excised at 0 hours, 2 hours, 3 days and 14 days post-injury. Transcription profiling of skin excised from thermal injured mouse to investigate the molecular mechanism of murine dermal burn wound.
2007-11-07 | E-GEOD-460 | 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:The study was designed to determine the differential gene expression occurring in burn eschar tissue in comparison to normal skin
2020-04-30 | GSE139028 | GEO