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.
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View SamplesDuring neocortical development, neurons undergo polarization, oriented migration, and layer type-specific differentiation. The transcriptional programs underlying these processes are not completely understood. Here we show that the transcription factor Bcl11a regulates polarity and migration of upper layer neurons. Bcl11a-deficient late-born neurons fail to correctly switch from multipolar to bipolar morphology resulting in impaired radial migration. We show that the expression of Sema3c is increased in migrating Bcl11a-deficient neurons and that Bcl11a is a direct negative regulator of Sema3c transcription. In vivo gain-of-function and rescue experiments demonstrate that Sema3c is a major downstream effector of Bcl11a required for the cell polarity switch and for the migration of upper layer neurons. Our data uncover a novel Bcl11a/Sema3c-dependent regulatory pathway used by migrating cortical neurons.
Bcl11a (Ctip1) Controls Migration of Cortical Projection Neurons through Regulation of Sema3c.
Specimen part
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 SamplesMouse sinoatrial node transcriptome
RNA sequencing of mouse sinoatrial node reveals an upstream regulatory role for Islet-1 in cardiac pacemaker cells.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Basonuclin-1 modulates epithelial plasticity and TGF-β1-induced loss of epithelial cell integrity.
Specimen part, Cell line
View SamplesPrevious studies suggest that there may be age and gender related differences in salivary gland function. However, the limited and often conflicting information available from healthy populations makes it difficult to confirm these differences. The purpose of the present study was to evaluate and compare changes in gene expression associated with age and gender in the human parotid gland. Differential expression, defined as statistically significant differences with at least 1.5 fold changes, was detected using the Affymetrix GeneChip HGU133plus2.0 microarray in 787 gene probe sets; 320 showed higher expression in males, while 467 showed higher expression in females. Several genes associated with saliva secretion were differentially expressed in male and female parotid gland including vesicle-associated membrane protein 3 VAMP3, synaptosomal-associated protein SNAP23, RAS oncogene family member RAB1A, syntaxin binding protein STXBP1. When the gene expression results from the youngest (19-38 years old) and the oldest (65-69 years old) female subjects were further evaluated, it was found that the expression of 228 genes were altered during aging; 155 genes were down-regulated, whereas 73 genes were up-regulated in the female parotid gland. Of the genes that were altered during aging, 24 of the 28 genes (86%) classified as being associated with immune responses were down-regulated in the aged parotid gland. A panel of differentially expressed, age- and gender-related genes was selected for further study by quantitative, real-time RT-PCR. Comparable differences in gene expression were detected by both Affymetrix array and quantitative, real-time RT-PCR methods. Taken together, our data suggest that salivary gland function may be adversely affected in the aged population due, at least in part, to the down regulation of several categories of genes. Moreover, the gender specific gene expressions identified in the present study correlates with the previously observed sexual dimorphism in salivary gland function.
Age and gender related differences in human parotid gland gene expression.
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View SamplesTGF-b1-stimulation induces an epithelial dedifferentiation-process, throughout which epithelial cell sheets disintegrate and gradually switch into fibroblastic-appearing cells (EMT-like transition). The purpose of these profiles was to identify differentially expressed genes that are regulated transcriptionally. Standard microarry-based gene expression profiles measure steady-state RNA but do not provide insight into underlying regulatory principles. NIAC-NTR-based gene expression profiling (Kenzelmann et al., PNAS, 2007) essentially enables the dissection of transcriptionally versus non-transcriptionally regulated genes within respective analysed time-frames. Briefly, NIAC-NTR relies on incorporation of 4sU (thio-uridine) into nascent RNA, which can subsequently be specifically isolated by custom-made columns. Total- and enriched (4sU-labeled) are then further processed for microarray gene expression profiling by standard procedures. This dataset complements previously released data of NIAC-NTR-based gene expression profiling of cells treated with TGF-b1 and 4sU for 2hrs [GSE23833].
Basonuclin-1 modulates epithelial plasticity and TGF-β1-induced loss of epithelial cell integrity.
Specimen part, Cell line
View SamplesTGF-b1-stimulation induces an epithelial dedifferentiation-process, throughout which epithelial cell sheets disintegrate and gradually switch into fibroblastic-appearing cells (EMT-like transition). Several transcription factors, some of them being TGF-b1-responsive, are functionally involved in such a switch and affect epithelial differentiation and plasticity.
Basonuclin-1 modulates epithelial plasticity and TGF-β1-induced loss of epithelial cell integrity.
Specimen part, Cell line
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