Dermal lymphatics form a network that connects all the hair follicles in skin and localize in proximity to the Hair Follicle Stem Cell. RNA sequencing analyses of isolated dermal lymphatics at two different time points of the hair follicle cycle (P55 and P70) indicate the existence of dynamic signaling networks associated with lymphatic remodeling, immune trafficking, and HF signaling. Overall design: Prox1CreERT2; ROSA26-LSL-eYFP mice of P55 (Mid Telogen) and P70 (Late telogen) were sacrificed and eYFP positive cells were isolated from the backskin.
Lymphatic vessels interact dynamically with the hair follicle stem cell niche during skin regeneration in vivo.
Treatment, Subject
View SamplesWe used microarrays to identify genes differentially expressed in EBV-infected human B cells supporting lytic replication vs. those refractory to EBV lytic replication.
Signal transducer and activator of transcription 3 limits Epstein-Barr virus lytic activation in B lymphocytes.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions.
Sex, Age, Specimen part, Treatment, Subject
View SamplesEnvironmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanism is unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists upregulated inflammation. Similarly, AhR signaling via the endogenous FICZ ligand reduced the inflammatory response in the imiquimod-induced model of psoriasis and AhR deficient mice exhibited a substantial exacerbation of the disease, compared to AhR sufficient controls. Non-haematopoietic cells, in particular keratinocytes, were responsible for this hyper-inflammatory response, which involved increased reactivity to IL-1beta and upregulation of AP-1 family members of transcription factors. Thus, our data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory disorders. Overall design: Total RNA obtained from skin explants taken from psoriatic patients or healthy donors cultured in the presence of AhR agonist or antagonist
Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions.
No sample metadata fields
View SamplesEnvironmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanism is unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists upregulated inflammation. Similarly, AhR signaling via the endogenous FICZ ligand reduced the inflammatory response in the imiquimod-induced model of psoriasis and AhR deficient mice exhibited a substantial exacerbation of the disease, compared to AhR sufficient controls. Non-haematopoietic cells, in particular keratinocytes, were responsible for this hyper-inflammatory response, which involved increased reactivity to IL-1beta and upregulation of AP-1 family members of transcription factors. Thus, our data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory disorders.
Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions.
Specimen part
View SamplesDifferential gene expression was analyzed for FACS sorted Math1::Cre; ROSA-tdTomato from hand dissected cochlear nuclei of wild type and Hoxa2/Hoxb2 mutant mice Overall design: In order to investigate the role of Hoxa2 and Hoxb2 transcription factors in a subset of cells of the cochlear nucleus, we generated double conditional knock-out by crossing the deleter line Math1::Cre crossed with Rosa tdTomato; Hoxa2fl/fl; Hoxb2fl/fl and Rosa tdTomato wild type background. FACS sorted cells from hand dissected cochlear nuclei were than processed and RNA-seq performed (see extract protocol and library construction protocol).
Hox2 Genes Are Required for Tonotopic Map Precision and Sound Discrimination in the Mouse Auditory Brainstem.
No sample metadata fields
View SamplesReprogramming somatic cells to induced pluripotency by Yamanaka factors is usually slow and inefficient, and is thought to be a stochastic process. We identified a privileged somatic cell state, from which acquisition of pluripotency could occur in a non-stochastic manner. Subsets of murine hematopoietic progenitors are privileged, whose progeny cells predominantly adopt the pluripotent fate with activation of endogenous Oct4 locus after 4-5 divisions in reprogramming conditions. Privileged cells display an ultrafast cell cycle of ~8 hours. In fibroblasts, a subpopulation cycling at a similar ultrafast speed is observed after 6 days of factor expression, and is increased by p53-knockdown. This ultrafast-cycling population accounts for >99% of the bulk reprogramming activity in wildtype or p53-knockdown fibroblasts. We compared the transcriptomes of the fast cycling cells with those of slower hematopoietic progenitors, bulk fibroblasts and established iPS cells. Overall design: 3-5 replicates for each of the six cell types were included: 4 replicates for established iPS cells, 4 replicates for bulk mouse embryonic fibroblasts (MEF), 4 replicates for fast cycling MEF, 4 replicates for slow cycling MEF, 5 replicates for fast cycling granulocyte monocyte progenitors (GMP) and 3 replicates for slow cycling GMP.
Nonstochastic reprogramming from a privileged somatic cell state.
No sample metadata fields
View SamplesOxidative stress as a result of cigarette smoking is an important etiological factor in the pathogenesis of chronic obstructive pulmonary disease (COPD), a chronic steroid-insensitive inflammatory disease of the airways. The activity of the transcriptional co-repressor Histone deacetylase-2 (HDAC2) is dramatically reduced in COPD and cells exposed to oxidative stress or cigarette smoke. Moreover, curcumin (diferuloylmethane), a dietary polyphenol, at concentrations upto 1uM specifically restores cigarette smoke extract (CSE)- or oxidative stress- impaired HDAC2 activity. The aim of this study was to therefore identify any links through those gene sets that are affected by oxidative stress and subsequent treatment with curcumin in order to determine whether or not this could explain the impact of curcumin on restoration of oxidant impaired HDAC2 transcriptional co-repressor activity.
Curcumin restores corticosteroid function in monocytes exposed to oxidants by maintaining HDAC2.
No sample metadata fields
View SamplesKeratinocytes isolated from one healthy donor were stimulated in triplicate for 24h with IL-36a, IL-36ß or IL-36? Overall design: Gene expression profile of IL-36 stimulated keratinocytes
An analysis of IL-36 signature genes and individuals with <i>IL1RL2</i> knockout mutations validates IL-36 as a psoriasis therapeutic target.
Specimen part, Subject
View SamplesCase report of a twin pair with concordant JMML, but with a different disease course predicted by gene expression profiling
Different outcomes of allogeneic hematopoietic stem cell transplant in a pair of twins affected by juvenile myelomonocytic leukemia.
Specimen part, Disease
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