Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA230718 | ENA |
REPOSITORIES: ENA
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Project description:Cell-Cell communication between skinkeratinocytes and fibroblats is non-redundantly coded through inflammatory cytokines
| PRJNA1131830 | ENA
Project description:Cell-cell communication between keratinocytes and fibroblasts is essential for skin homeostasis, regulation and regeneration. How extracellular cytokine signaling, intra-cellular protein signaling and transcriptional regulation initiate and maintain this communication is still largely unknown. Here, we study in vitro the secretome and transcriptome dynamics that establish double paracrine cell-cell communication between primary human keratinocytes and fibroblasts. We find that keratinocyte-derived interleukin 1α initiates the cell communication, eliciting a constitutive NF-κB-mediated inflammation response in the fibroblasts. Their resulting transcriptome response over at least 12 hours induces a fibroblast secretome capable of enhancing keratinocyte migration. Applying partial least square regression to secretome perturbation experiments using recombinant proteins or antibodies demonstrates the synergistic interaction of early and late secreted inflammatory CC and CXC chemokines as well as IL6, whose relative composition directly controls keratinocyte migration. Conversely, inhibiting individual cytokines during cell-communication abrogates the keratinocyte phenotype. Hence, only the simultaneous activity of multiple inflammatory cytokines together with prolonged inflammatory response in the fibroblasts lead to increased keratinocyte migration after double paracrine cell communication, putatively serving as safeguard mechanisms for proper skin regeneration.
2019-10-22 | GSE53037 | GEO
Project description:Cell-cell communication between keratinocytes and fibroblasts is essential for skin homeostasis, regulation, and regeneration. How extracellular cytokine signaling, intracellular protein signaling and transcriptional regulation initiate and maintain this communication is still largely unknown. Here, we study in vitro the secretome and transcriptome dynamics that establish double paracrine cell-cell communication between normal human keratinocytes (NHK) and human dermal fibroblasts (HDF). To mimic double paracrine stimulation, we stimulate HDF with NHK-conditioned medium for 18 hours and use the then HDF-conditioned medium to stimulate the NHK. The NHK response is quantified at different timepoints for a duration of up to 24 hours. We find that double paracrine stimulation changes extracellular matrix composition and activates translation and enhances keratinocyte migration.
2024-07-05 | GSE271501 | GEO
Project description:To understand the role of epidermal keratinocytes in immunopathology of skin diseases with predominant T helper (Th) cell responses, we measured the genome-wide transcriptional profile of human keratinocytes in response to IFNgamma, IL-4, IL-17A or IL-22, major cytokines produced by Th1, Th2, Th17 or Th22 cells, respectively. IL-6 was also included in the transcriptional profile analysis because a variety of pro-inflammatory stimuli stimulate human keratinocytes to produce IL-6 that has an autocrine or paracrine role in epidermal immunity. We aimed to discover commonly expressed genes in human keratinocytes in response to pro-inflammatory cytokines, which would be associated with common pathophysiological responses in various skin diseases such as skin permeability barrier disruption or epidermal hyperplasia. Normal human keratinocytes (NHKs) were stimulated with IFNγ, IL-4, IL-6, IL-17A and IL-22 for 24 hours and harvested for total RNA extraction and hybridization on Affymetrix microarrays.
2014-10-02 | E-GEOD-53751 | biostudies-arrayexpress
Project description:The immunopathogenesis of psoriasis, a common chronic inflammatory disease of the skin, is incompletely understood. Here we demonstrate, using a combination of single cell and spatial RNA sequencing, IL-36 dependent amplification of IL-17A and TNF inflammatory responses in the absence of neutrophil proteases, which primarily occurred within the supraspinous layer of the psoriatic epidermis. We further show that a subset of SFRP2+ fibroblasts in psoriasis contribute to amplification of the immune network through transition to a pro-inflammatory state. The SFRP2+ fibroblast communication network involves production of CCL13, CCL19 and CXCL12, connected by ligand-receptor interactions to other spatially proximate cell types: CCR2+ myeloid cells, CCR7+ LAMP3+ dendritic cells, and CXCR4 expressed on both CD8+ Tc17 cells and keratinocytes, respectively. The SFRP2+ fibroblasts also express cathepsin S, further amplifying inflammatory responses by activating IL-36G in keratinocytes. These data provide an unprecedented view of psoriasis pathogenesis, which expands our understanding of the critical cellular participants to include inflammatory fibroblasts and their cellular interactions.
2023-05-07 | GSE225475 | GEO
Project description:Aging is characterized by a gradual decline in function, partly due to molecular damage that accumulates over time. Human skin is highly susceptible to both chronological aging and environmental damage in the form of UV photoaging. This results in detrimental structural and physiological changes with age. In this study we sought to comprehensively address both chronological and photoaging at the single-cell level, and to explore genetic and environmental factors, revealing their influences on the aging process. We included samples from young, middle-aged, and old individuals, and with these samples, we compared chronological aging and photoaging. Utilizing single-cell RNA sequencing, we created a comprehensive human skin cell atlas, that offers insights into the cellular composition and functions. We investigated the renewal ability of epidermis stem cells as they age and extended the study to fibroblasts, hair follicles, and endothelial cells. Examining the genetic landscape of aging in keratinocytes, we identified two distinct "gene modules" with altered gene expression during aging. Furthermore, we uncovered that skin aging involves interactions between epidermal keratinocytes and dermal fibroblasts, as well as extensive communication of keratinocytes with various other skin cell types as revealed through ligand-receptor pairs. Interactions, such as COL17A1-A1b1complex, highlighted a direct link between keratinocytes and fibroblast stimulation for collagen production. Most importantly, A key gene, MYO1, associated with skin aging was identified, leading to the development of an innovative mRNA treatment aimed at promoting skin rejuvenation by targeting this gene. Experimental results demonstrated that the mRNA treatment reduces basal stem cell senescence, increases basal stem cell proliferation, and enhances collagen production in fibroblasts via keratinocyte-fibroblast communication. The MYO1-targeted treatment is validated as an effective strategy for reversing skin aging by targeting cellular mechanisms.
2024-11-18 | GSE274955 | GEO
Project description:Lichen planus (LP) is a chronic, debilitating, inflammatory disease of the skin and mucous membranes that affects 1-2% of Americans. Its molecular pathogenesis remains poorly understood, and there are no FDA-approved treatments. We performed single cell RNA sequencing on blood and affected and unaffected skin from 7 LP patients. LP affected skin exhibited a robust immune infiltrate primarily composed of CD8 T-cells. These cells were specifically recruited by cytokines secreted by both superficial and dermal layers of skin. Basal keratinocytes and fibroblasts secrete CXCL9 and CXCL10, and fibroblasts secrete CCL19. Molecular analysis of LP skin and blood samples increased our understanding of disease pathogenesis and identified CCL19 as a new therapeutic target for treatment.
2024-10-03 | GSE254542 | GEO
Project description:Skin is usually exposed during human exposures to ionizing radiation, however there are few experiments that evaluate the radiation responsiveness of the cells of the epidermis (keratinocytes) and those of the dermis (fibroblasts) in the same studies. We evaluated the transcriptional responses of quiesent primary keratinocytes and fibroblasts from the same individual and compared them with quiescent keratinocytes and fibroblasts that were immortalized by human telomerase (hTert). The primary transcriptional responses to 10-500 cGy ionizing radiation were p53-mediated responses; however, we did identify distinct responses between the keratinocytes and the fibroblasts. Experiment Overall Design: Four cell types (primary keratinocytes, hTert immortalized keratinocytes, primary fibroblasts, hTert immortalized fibroblasts) grown to quiescence, treated with 0, 10, 100 or 500 cGy gamma irradiation, RNA collected at 4 hrs.
2009-06-08 | E-GEOD-14466 | biostudies-arrayexpress
Project description:Background: Atopic dermatitis (AD) is a common inflammatory skin disease with a TH2 immune polarity and is often colonized with Staphylococcus aureus. Despite recent advances in understanding Staphylococcus species infection and the impact of polar TH cytokines on the skin, the interactions between these factors in AD pathology are poorly understood. Methods: AD-related key immune biomarkers were measured by quantitative real-time PCR in human keratinocytes exposed heat-killed S. epidermidis or S. aureus with/without polar T-cell derived cytokines such as IFN-γ (TH1), IL-4/IL-13 (TH2), and IL-22 (TH22). Further analysis was performed by RNA-sequencing to define broader responses in both Staphylococcus species and polar cytokines. The similarity of gene expression patterns in AD skin lesions and stimulated keratinocytes was evaluated by gene-set variation analysis (GSVA). Results: Gene expression analysis exhibited distinct immune responses in keratinocytes depending on individual bacterial or polar cytokine exposure. Besides, numerous genes were synergistically upregulated by the combination exposure of bacteria and polar TH cytokines. Moreover, GSVA revealed that combined exposure of S. aureus and IL-4 + IL-13 exhibited significantly higher correlations with a genomic signature of AD skin lesions than their single exposure or combinations of other polar TH cytokines. Conclusions: Our findings provide novel insights into AD-related transcriptional activation and illustrate a potentially novel pathogenic function of S. aureus and IL-4/IL-13 interactions in AD.
2021-12-31 | GSE173902 | GEO
Project description:Skin is usually exposed during human exposures to ionizing radiation, however there are few experiments that evaluate the radiation responsiveness of the cells of the epidermis (keratinocytes) and those of the dermis (fibroblasts) in the same studies. We evaluated the transcriptional responses of quiesent primary keratinocytes and fibroblasts from the same individual and compared them with quiescent keratinocytes and fibroblasts that were immortalized by human telomerase (hTert). The primary transcriptional responses to 10-500 cGy ionizing radiation were p53-mediated responses; however, we did identify distinct responses between the keratinocytes and the fibroblasts. Keywords: keratinocytes and fibroblasts - dose response to ionizing radiation
2009-05-31 | GSE14466 | GEO