Alopecia areata (AA) is a prevalent disease associated with major emotional distress, and lacks effective, safe therapeutics for patients with extensive hair loss. This is the first report of hair regrowth with specific cytokine antagonism, in three patients with extensive hair loss ranging from 40% scalp involvement to alopecia universalis. Ustekinumab, an IL-12/23p40 antagonist that is highly effective in psoriasis, showed impressive ability to induce hair regrowth, coupled with suppression of inflammatory pathways and upregulation of hair keratins. Our report suggests that extensive AA is reversible using targeted treatments, opening the door for specific cytokine antagonism for this debilitating disease.
Extensive alopecia areata is reversed by IL-12/IL-23p40 cytokine antagonism.
Sex, Specimen part, Disease stage, Subject, Time
View SamplesWe conducted a randomized, double-blind, placebo-controlled trial in adults with moderate-to-severe AD unresponsive to conventional topical or systemic treatment. Fezakinumab (ILV-094; anti IL-22 monoclonal antibody) monotherapy was administered for 12 weeks (primary endpoint), and clinical responses were followed until week 20. AD transcriptome significantly improved at week 12 in fezakinumab vs. placebo (p<1E-18).
Baseline IL-22 expression in patients with atopic dermatitis stratifies tissue responses to fezakinumab.
Specimen part, Treatment, Subject
View SamplesMicroarray Analysis of Space-flown Murine Thymus Tissue Reveals Changes in Gene Expression Regulating Stress and Glucocorticoid Receptors. We used microarrays to detail the gene expression of space-flown thymic tissue and identified distinct classes of up-regulated genes during this process. We report here microarray gene expression analysis in young adult C57BL/6NTac mice at 8 weeks of age after exposure to spaceflight aboard the space shuttle (STS-118) for a period of 13 days. Upon conclusion of the mission, thymus lobes were extracted from space flown mice (FLT) as well as age- and sex-matched ground control mice similarly housed in animal enclosure modules (AEM). mRNA was extracted and an automated array analysis for gene expression was performed. Examination of the microarray data revealed 970 individual probes that had a 1.5 fold or greater change. When these data were averaged (n=4), we identified 12 genes that were significantly up- or down-regulated by at least 1.5 fold after spaceflight (p0.05). Together, these data demonstrate that spaceflight induces significant changes in the thymic mRNA expression of genes that regulate stress, glucocorticoid receptor metabolism, and T cell signaling activity. These data explain, in part, the reported systemic compromise of the immune system after exposure to the microgravity of space.
Microarray analysis of spaceflown murine thymus tissue reveals changes in gene expression regulating stress and glucocorticoid receptors.
Specimen part
View SamplesIn this study, we analyzed the impact of a mutation in the wrn-1 gene compared to wild type worms and the dietary supplementation of vitamin C on the global mRNA expression of the whole C. elegans by the RNA-seq technology. Overall design: Whole C. elegans mRNA profiles at the L4 stage of wild type and wrn-1(gk99) mutant animals treated with or without 10 mM ascorbate were generated by deep sequencing, in triplicate, using the HiSeq 2000 machine form Illumina. Detailed statistics on the quality of the reads were calculated with FastQC (http://www.bioinformatics.babraham.ac.uk/projects/fastqc/). The 50 base pairs raw sequences were aligned on the C. elegans ce10/W220 genome with TopHat using the Ensembl annotations provided with the Illumina iGenomes. The htseq-count software (http://www-huber.embl.de/users/anders/HTSeq) was used to count the number of reads aligned to each gene. These counts were then normalized relative to the sequencing depth with DESeq.
Expression profile of Caenorhabditis elegans mutant for the Werner syndrome gene ortholog reveals the impact of vitamin C on development to increase life span.
Specimen part, Treatment, Subject
View SamplesRegulatory T (Treg) cells play an indispensable role in immune homeostasis. The development and function of Tregs are dependent on transcriptional factor Foxp3, but how constant expression of Foxp3 is maintained in Tregs is not clear. Here we show that ablation of the conserved non-coding DNA sequence 2 (CNS2) at the Foxp3 locus in mice led to spontaneous lymphoproliferative disease and exacerbation of experimental autoimmune encephalomyelitis (EAE). CNS2 is required for activated Treg cells to maintain elevated Foxp3 expression, which is critical for their suppressor function and lineage stability. Mechanistically, upon TCR stimulation, NFAT binds to both CNS2 and Foxp3 promoter and mediates the interaction between CNS2 and Foxp3 promoter. Our findings demonstrated an essential role for CNS2 in maintaining the stability and function of activated Treg cells and identified NFAT as a key mediator of its function. Overall design: Gene expression was profiled in T regulatory cells (Treg) in WT and CNS2 knockout mice. CNS2 knockout mice lack a conserved non-coding DNA sequence 2 (CNS2) at the Foxp3 locus. Treg cells were further sorted into Foxp3-high and Foxp3-low populations based on the expression level of Foxp3. mRNA was profiled using RNA-Seq (unstranded, polyA+, SE100) in replicate for each condition
Function of a Foxp3 cis-element in protecting regulatory T cell identity.
No sample metadata fields
View SamplesThe RNA-binding protein FUS is implicated in transcription, alternative splicing of neuronal genes and DNA repair. Mutations in FUS have been linked to human neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis). We genetically disrupted fus in zebrafish (Danio rerio) using the CRISPR-Cas9 system. The fus knockout animals are fertile and did not show any distinctive phenotype. Mutation of fus induces mild changes in gene expression on the transcriptome and proteome level in the adult brain. We observed a significant influence of genetic background on gene expression and 3’UTR usage, which could mask the effects of loss of Fus. Unlike published fus morphants, maternal zygotic fus mutants do not show motoneuronal degeneration and exhibit normal locomotor activity. Overall design: We performed paired-end sequencing (100bp reads) of the polyA+ transcriptome from brains of five individuals with Fus-/- genotype and four with Fus wild type genotype. Note on RNA-Seq replicates: after performing first RNA sequencing on four replicates of Fus-/- and WT (labeled with the prefix "Sample_imb_ketting_2014_13_") we received a notice from Illumina stating a problem with the library preparation kit lot that was used to prepare the libraries. Due to that, we performed RNA sequencing a second time, using the same input RNA, except for the Fus knockout replicate #3, because there was not enough input RNA left. Instead, a different Fus knockout replicate (#1) was sequenced. However, we compared the mapped reads from sequencing run 1 and sequencing run 2 using plotCorrelaction from DeepTools, and the samples are highly correlated (at least 0.97 and 0.95, Spearman and Pearson correlation respectively). Therefore, we considered first ("Sample_imb_ketting_2014_13_") and second sequencing runs as technical replicates.
Characterization of genetic loss-of-function of Fus in zebrafish.
No sample metadata fields
View SamplesForeign body reaction (FBR), initiated by adherence of macrophages to biomaterials, is associated with several complications.
Gene expression study of monocytes/macrophages during early foreign body reaction and identification of potential precursors of myofibroblasts.
Specimen part
View SamplesC2C12 cells expressing constitutively active hN1?ECD were activated by complete DAPT washout for 1h or 6h, or left in 10 uM DAPT Overall design: 2 Samples and 1 Control
Dynamic Ligand Discrimination in the Notch Signaling Pathway.
Specimen part, Subject
View SamplesTranscriptional profiling of histone methyltransferase SUV39H1-selective small molecule inhibitor F5446-induced genes in human colon carcinoma cells. Tumor cells were treated with F5446 for 48h and used for RNA isolation. The treated cells were compared to untreated control cells. The objective is to identify genes that are regulated by H3K9me3 in the metastatic human colon carcinoma cells.
SUV39H1 regulates human colon carcinoma apoptosis and cell cycle to promote tumor growth.
Treatment
View Samplesaffy_pop_2011_08 - poplar bent study - genes regulated by PtaZFP2 in absence of mechanical stress - genes regulated by PtaZFP2 after one bending.Species: Populus tremula x Populus alba-- The laboratory previously established a poplar transgenic line overexpressing PtaZFP2 under the control of an estradiol-inducible promoter. - the experiment, conducted on 3-month-old hydroponically-grown poplars, consists in the comparison of WT poplars treated with estradiol and the PtaZFP2-overexpressing line treated with estradiol. We also compared unbent and bent PtaZFP2-overexpressing poplars. The applied strain is quantitatively controlled (Coutand & Moulia, 2000, JExpBot; coutand et al., 2009, Plant Physiology) -
The zinc finger protein PtaZFP2 negatively controls stem growth and gene expression responsiveness to external mechanical loads in poplar.
Treatment
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