Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA229755 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1036423.fastq.gz | Fastqsanger.gz | |||
| SRR1036424.fastq.gz | Fastqsanger.gz | |||
| SRR1036425.fastq.gz | Fastqsanger.gz | |||
| SRR1036426.fastq.gz | Fastqsanger.gz | |||
| SRR1036427.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
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Project description:Whether epidermal factors play a primary role in immune-mediated skin diseases such as psoriasis is unknown. We now show that the pro-differentiation transcription factor Grainyhead-like 3 (GRHL3), essential during epidermal development but dispensable in adult skin homeostasis, is required for barrier repair after adult epidermal injury. Consistent with activation of a GRHL3-regulated repair pathway in psoriasis, we find GRHL3 up-regulation in lesional skin where GRHL3 binds known epidermal differentiation gene targets. Furthermore, we show the functionality of this pathway in the Imiquimod mouse model of immune-mediated epidermal hyperplasia where loss of Grhl3 exacerbates the epidermal damage response, conferring greater sensitivity to disease induction, delayed resolution of epidermal lesions, and resistance to anti-IL-22 therapy. ChIP-seq and gene expression profiling studies show that while GRHL3 regulates differentiation genes both in development and during repair from immune-mediated damage, it targets distinct sets of genes in the two processes. In particular, GRHL3 suppresses a number of alarmin and other pro-inflammatory genes after immune injury. This study identifies a GRHL3-regulated epidermal barrier repair pathway that suppresses disease initiation and helps resolve existing lesions in immune-mediated epidermal hyperplasia. A single timepoint was assessed after physical injury of the epidermal barrier and two timepoints were assessed after immune mediated injury of the epidermis following Imiquimod treatment (psoriasis mouse model)
2014-10-01 | E-GEOD-59384 | biostudies-arrayexpress
Project description:Whether epidermal factors play a primary role in immune-mediated skin diseases such as psoriasis is unknown. We now show that the pro-differentiation transcription factor Grainyhead-like 3 (GRHL3), essential during epidermal development but dispensable in adult skin homeostasis, is required for barrier repair after adult epidermal injury. Consistent with activation of a GRHL3-regulated repair pathway in psoriasis, we find GRHL3 up-regulation in lesional skin where GRHL3 binds known epidermal differentiation gene targets. Furthermore, we show the functionality of this pathway in the Imiquimod mouse model of immune-mediated epidermal hyperplasia where loss of Grhl3 exacerbates the epidermal damage response, conferring greater sensitivity to disease induction, delayed resolution of epidermal lesions, and resistance to anti-IL-22 therapy. ChIP-seq and gene expression profiling studies show that while GRHL3 regulates differentiation genes both in development and during repair from immune-mediated damage, it targets distinct sets of genes in the two processes. In particular, GRHL3 suppresses a number of alarmin and other pro-inflammatory genes after immune injury. This study identifies a GRHL3-regulated epidermal barrier repair pathway that suppresses disease initiation and helps resolve existing lesions in immune-mediated epidermal hyperplasia.
2014-10-01 | GSE59384 | GEO
Project description:Epidermal barrier repair mechanisms activated in psoriasis lesions are likely involved in limiting the severity of this disease. We show that loss of grainyhead-like 3 (Grhl3), a pro-terminal differentiation factor in the epidermis, is sufficient to trigger greater sensitivity to and delayed resolution of epidermal lesions resulting from either physical or immune mediated barrier injury. After stimulation of Toll like receptors, the loss of Grhl3 resulted in increased epidermal damage with a striking increase in basal cell proliferation, hyperplasia of partially differentiated suprabasal layers, and a transcriptional profile highlighted by the overexpression of epidermal wound response and alarmin genes. This study reveals an important role for the epidermis in the initiation and recovery from immune-mediated lesions, and indicated that the epidermal regulator Grhl3 acts to both suppress disease initiation and resolve existing lesions. This work suggests that treatments focused on improving barrier function could be used preventatively and therapeutically in psoriasis. Whole skin was collected from E16.5 mouse backskins for Grhl3 ChIP. Adult epidermis for depilation and imiquimod experiments was seperated from dermis using dispase prior to Grhl3 ChIP.
2014-09-01 | E-GEOD-52648 | biostudies-arrayexpress
Project description:Epidermal barrier repair mechanisms activated in psoriasis lesions are likely involved in limiting the severity of this disease. We show that loss of grainyhead-like 3 (Grhl3), a pro-terminal differentiation factor in the epidermis, is sufficient to trigger greater sensitivity to and delayed resolution of epidermal lesions resulting from either physical or immune mediated barrier injury. After stimulation of Toll like receptors, the loss of Grhl3 resulted in increased epidermal damage with a striking increase in basal cell proliferation, hyperplasia of partially differentiated suprabasal layers, and a transcriptional profile highlighted by the overexpression of epidermal wound response and alarmin genes. This study reveals an important role for the epidermis in the initiation and recovery from immune-mediated lesions, and indicated that the epidermal regulator Grhl3 acts to both suppress disease initiation and resolve existing lesions. This work suggests that treatments focused on improving barrier function could be used preventatively and therapeutically in psoriasis.
2014-09-01 | GSE52648 | GEO
Project description:Background: Atopic dermatitis (AD) is a common inflammatory skin disease exhibiting a predominantly Th2/"T22" immune activation and a defective epidermal barrier. Narrow-band UVB (NB-UVB) is considered an efficient treatment for moderate to severe AD. In psoriasis, NB-UVB has been found to suppress the Th1/Th17 immune polarization with subsequent reversal of epidermal hyperplasia. The immunomodulatory effects of this treatment are largely unknown in AD. Our study evaluates the effects of NB-UVB on immune and barrier abnormalities in AD, aiming to establish reversibility of disease and biomarkers of therapeutic response. Methods: 12 moderate-to-severe chronic AD patients received NB-UVB phototherapy 3 times weekly for up to 12 weeks. Lesional and non-lesional skin biopsies were obtained before and after treatment and evaluated by gene-expression and immunohistochemistry studies. Results: All patients had at least a 50% reduction in SCORing of AD (SCORAD) index with NB-UVB phototherapy. The Th2, T22, and Th1 immune pathways were suppressed and measures of epidermal hyperplasia and differentiation also normalized after phototherapy. The reversal of disease activity was associated with elimination of inflammatory leukocytes, Th2/"T22"-associated cytokines and chemokines, and normalized expression of barrier proteins. Conclusions: Our study shows reversal of both the epidermal defects and underlying immune activation in AD. By determining the correlation of variables with therapeutic response, we have defined a set of biomarkers of disease response that associate resolved Th2 and T22 inflammation with reversal of barrier pathology. This data supports the "inside-out" hypothesis of AD, suggesting that it is a disease primarily driven by an immune stimulus. genomic profiling of treatment effect of NB-UVB in AD in both lesional and non-lesional AD skin from 10 patients. Treatment effect, disease state analysis
2011-07-01 | E-GEOD-27887 | biostudies-arrayexpress
Project description:The epidermal barrier protects the body against mechanical injury, infection and dehydration. The respective contribution of type I and type II keratins which form the major cytoskeleton in epidermal keratinocytes in barrier formation and stress protection is incompletely understood. Here, we reveal a novel mechanism by which keratins control anti-oxidant responses through barrier-dependent and cell-autonomous mechanisms. Mice lacking the entire type I (KtyI) or type II (KtyII) keratin gene clusters suffer from distinct prenatal barrier defects. Comparative transcriptome profiling identifies essential cornified envelope components and reveals strong upregulation of the bZIP transcription factor Nrf2 in situ. Isolated keratinocytes from both strains of mice show elevated mitochondrial oxygen consumption and Nrf2 activity, decreased upon keratin re-expression. We propose a model in which keratins control mitochondria-derived oxidative stress via Nrf2 activation. Our findings reveal major contributions of keratins to chronic inflammation and autoimmune disorders. Total RNA obtained from E18.5 embryo back skin from typeI and II keratin knockout compared with respective wild type.
2016-03-26 | E-GEOD-79590 | biostudies-arrayexpress
Project description:Formation and maintenance of an epithelial barrier is essential for defense against fungal invasion and other noxious stimuli and is fundamental to the survival of all animals. As part of homeostatic repair mechanisms, mucosal tissues eliminate damaged epithelial cells while trying to preserve barrier function. Compromised epithelial integrity following trauma is a common mode of infection, and therefore, enhancing mucosal repair may help to mitigate opportunistic invasion. However, the technical challenges to efficiently manipulate and monitor mucosal injury in vivo has thus far prevented a detailed characterization and therapeutic exploitation of key epithelial repair mechanisms. Here we establish a high-throughput mucosal injury and repair model by inducible loss of epithelial cells in larval zebrafish. Transcriptional profiling identified a significant upregulation of the epidermal growth factor receptor ligand epigen (EPGN) upon tissue damage, and we found treatment with recombinant human EPGN suppressed epithelial cell loss to maintain barrier integrity in the face of damage. This study provides key insights into the mechanisms regulating epithelial cell loss during mucosal injury and identifies key pathways associated with rapid restoration of barrier function and epithelial tissue integrity.
2021-03-01 | GSE140839 | GEO
Project description:Defective permeability barrier is an important feature of many skin diseases and causes mortality in premature infants. To investigate the control of barrier formation, we characterized the epidermally expressed Grainyhead-like epithelial transactivator (Get-1)/Grhl3, a conserved mammalian homologue of Grainyhead, which plays important roles in cuticle development in Drosophila. Get-1 interacts with the LIM-only protein LMO4, which is co-expressed in the developing mammalian epidermis. The epidermis of Get-1(-/-) mice showed a severe barrier function defect associated with impaired differentiation of the epidermis, including defects of the stratum corneum, extracellular lipid composition and cell adhesion in the granular layer. The Get-1 mutation affects multiple genes linked to terminal differentiation and barrier function, including most genes of the epidermal differentiation complex. Get-1 therefore directly or indirectly regulates a broad array of epidermal differentiation genes encoding structural proteins, lipid metabolizing enzymes and cell adhesion molecules. Although deletion of the LMO4 gene had no overt consequences for epidermal development, the epidermal terminal differentiation defect in mice deleted for both Get-1 and LMO4 is much more severe than in Get-1(-/-) mice with striking impairment of stratum corneum formation. These findings indicate that the Get-1 and LMO4 genes interact functionally to regulate epidermal terminal differentiation. Experiment Overall Design: The same region of the mouse back skin was excised from three Get1 +/+ and three Get1 â/â mice at e18.5.
2007-12-13 | E-GEOD-7381 | biostudies-arrayexpress
Project description:Epidermal stem cells constantly rejuvenate the skin’s barrier, which excludes harmful microbes and prevents dehydration. In routine wounds, underlying hair follicle stem cells (HFSCs), normally dedicated to hair regeneration, must also reconstruct and thereafter maintain the overlying epidermis. How these fate choices are balanced to restore physiologic function to damaged tissue remains poorly understood. Here, we uncover the non-essential amino acid serine as a surprising rheostat in this process. Utilizing diet and HFSC-specific loss-of-function studies, we show that under serine-depleted conditions, HFSCs delay hair growth, and upon injury skew their fate towards epidermal re-epithelialization while concomitantly limiting hair growth. Combining temporal single-cell RNA sequencing, genetics and pharmacological intervention, we show that serine deficiency augments an injury-activated integrated stress response (ISR), boosting re-epithelization and rapidly restoring the skin’s barrier at the wound edge. Our findings integrate injury, the ISR, metabolism, tissue fate-selection and repair, offering potential for dietary and pharmacologic intervention to accelerate wound healing.
2024-06-20 | GSE270324 | GEO
Project description:Epidermal stem cells constantly rejuvenate the skin’s barrier, which excludes harmful microbes and prevents dehydration. In routine wounds, underlying hair follicle stem cells (HFSCs), normally dedicated to hair regeneration, must also reconstruct and thereafter maintain the overlying epidermis. How these fate choices are balanced to restore physiologic function to damaged tissue remains poorly understood. Here, we uncover the non-essential amino acid serine as a surprising rheostat in this process. Utilizing diet and HFSC-specific loss-of-function studies, we show that under serine-depleted conditions, HFSCs delay hair growth, and upon injury skew their fate towards epidermal re-epithelialization while concomitantly limiting hair growth. Combining temporal single-cell RNA sequencing, genetics and pharmacological intervention, we show that serine deficiency augments an injury-activated integrated stress response (ISR), boosting re-epithelization and rapidly restoring the skin’s barrier at the wound edge. Our findings integrate injury, the ISR, metabolism, tissue fate-selection and repair, offering potential for dietary and pharmacologic intervention to accelerate wound healing.
2024-06-20 | GSE270317 | GEO