To understand the global view of dysregulated genes and pathwyas in CRYAAN101D lenses, RNA sequencing of 2 & 4 months old CRYAAWT and CRYAAN101D lenses was carried out. Overall design: Determination of differential gene expression between CRYAAWT and CRYAAN101D in 2 & 4 months old lenses
Molecular mechanism of formation of cortical opacity in CRYAAN101D transgenic mice.
No sample metadata fields
View SamplesPropose: We used next-generation RNA sequencing (RNA-seq) to characterize the transcriptional changes in primary human melanocytes during recessive Cole disease. Our patient carried missense mutation in the ENPP1 gene (c.358T>C; p.C120R). RNA-seq was performed using mRNA extracted from primary hypo- and hyper-pigmented melanocytes isolated from affected patient and melanocytes from his healthy heterozygous sibling and an aged- and ethnicity-matched control. Results: A pairwise fold-change comparison was performed and genes were computationally filtered using a cutoff of more than 2 fold change and P<0.01. We first compared hyper-pigmented melanocytes to each control individually and then overlapped the results to obtain a list of 1041 up-regulated and 692 down-regulated genes. The same analysis was done for hypo-pigmented melanocytes to found that 535 genes were up-regulated and 520 were down-regulated. Finally, to obtain a profile of the overall differential gene expression, down-regulated genes in hyper and hypo-pigmented cells were overlapped to identify 143 genes that were down-regulated in patient melanocytes compared to controls regardless of pigmentation status. Similar analysis was performed to obtain the list of 172 up-regulated genes. We selected 36 deregulated genes, most of which were associated with melanocyte development and pigmentation signaling pathways, and validated 32 of them by Q-PCR, indicating that our RNA-Seq data was accurate and reliable. Conclusion: Our study represents the first analysis of hypo- and hyper-pigmented primary melanocytes isolated from affected patient versus healthy controls in recessive Cole disese pathology. Overall design: mRNA profiles of hyper- and hypo-pigmented mutant melanocytes, heterozygous and wild type melanocytes were sequenced in triplicate on the Hiseq 2500 High output 100PE
ENPP1 Mutation Causes Recessive Cole Disease by Altering Melanogenesis.
Sex, Age, Specimen part, Subject
View SamplesFrom over 300 patients two groups were selected which had prostate tumors with either well differentiated (WD) or poorly differentiated (PD) after radical Prostatectomy. The PD group had Gleason score 8-9, seminal vesicle invasion, and poorly differentiated tumor cells; the WD group had Gleason score 6-7, no seminal vesicle invasion, and well to moderately differentiated tumor cells. LCM compatible specimens were selected from age and race (Caucasians) matched PD or WD patients with no family history of CaP. Matching normal epithelal cells were also selected for the analysis.
Elevated osteonectin/SPARC expression in primary prostate cancer predicts metastatic progression.
Specimen part
View SamplesAffymetrix GeneChip Human Gene 1.0 ST Array was applied to compare the expression profiles in peripheral blood mononuclear cells(PBMC) between healthy controls and multiple sclerosis patients(MS pt).
Role of HDAC3 on p53 expression and apoptosis in T cells of patients with multiple sclerosis.
Specimen part, Disease, Disease stage
View SamplesThe activation of TLR-MyD88 (Toll like receptor- Myeloid differentiation factor 88) signaling within T cells functions as a potent costimulatory signal that boosts antitumor and antiviral responses. However, the molecular mechanisms underlying the costimulatory processes are poorly understood. We compared microarray gene analysis data between TLR1-TLR2 stimulated and unstimulated T cell receptor transgenic pmel and MyD88-/-pmel CD8+ T cells and identified changes in the expression levels of several TNF family members. In particular, TLR-stimulation increased 4-1BB levels in pmel but not in MyD88-/-pmel T cells. A link between 4-1BB and TLR1-TLR2 signaling in CD8+ T cells was highlighted by in fact that 4-1BB-/- T cells exhibited suboptimal responses to TLR1-TLR2 agonist, but responded normally to CD28 or OX40 costimulation. Moreover, blocking 4-1BB signaling with antibodies also hindered the costimulatory effects of the TLR1-TLR2 agonist. The elevated levels of 4-1BB transcripts in TLR1-TLR2stimulated cells were not due to increased mRNA stability nor increased histone activation but instead were associated with increased binding of p65 and c-Jun to two distinct 4-1BB promoter sites. Combining TLR1-TLR2 ligand with an agonistic anti-4-1BB antibody enhanced the antitumor activity in mice with established melanoma tumors. These studies reveal that the costimulatory effects of TLR1-TLR2 signaling in CD8+ T cells are in part mediated by 4-1BB and are important for mounting an effective antitumor immune response.
Cross-talk between 4-1BB and TLR1-TLR2 Signaling in CD8+ T Cells Regulates TLR2's Costimulatory Effects.
Specimen part
View SamplesJAK inhibitors like tofacitinib were thought to act primarily on T cells. However, our data and recent research suggest that JAK receptors are also present on keratinocytes. Here, we show effect of tofacitinib on primary keratinocytes, which could explain effects of topical tofacitinib treatment in psoriasis.
Tofacitinib Represses the Janus Kinase-Signal Transducer and Activators of Transcription Signalling Pathway in Keratinocytes.
Specimen part
View SamplesmicroRNAs are small non-coding RNAs that can affect gene expression. We used microarrays to analyze gene expression in miR-499 transgenic mouse hearts.
Elevated miR-499 levels blunt the cardiac stress response.
Specimen part
View SamplesThe Drosophila polypyrimidine tract-binding protein (dmPTB or hephaestus) plays an important role during spermatogenesis. The heph2 mutation in this gene results in a specific defect in spermatogenesis, causing aberrant spermatid individualization and male sterility. However, the array of molecular defects in the mutant remains uncharacterized. This study provides the first comprehensive list of genes misregulated in vivo in the heph2 mutant in Drosophila and offers insight into the role of dmPTB during spermatogenesis. Overall design: Two samples; Control and the heph2 mutant
High Throughput Sequencing Identifies Misregulated Genes in the Drosophila Polypyrimidine Tract-Binding Protein (hephaestus) Mutant Defective in Spermatogenesis.
Sex, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Blocking promiscuous activation at cryptic promoters directs cell type-specific gene expression.
Specimen part
View SamplesMouse sinoatrial node transcriptome
RNA sequencing of mouse sinoatrial node reveals an upstream regulatory role for Islet-1 in cardiac pacemaker cells.
No sample metadata fields
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