Lysosome-related organelles have versatile functions including protein and lipid degradation, signal transduction, and protein secretion. The molecular elucidation of rare congenital diseases affecting endosomal/lysosomal biogenesis has given insights into physiological functions of the innate and adaptive immune system.. Here, we describe a novel human primary immunodeficiency disorder and provide evidence that the endosomal adaptor protein p14, previously characterized as confining mitogen-activated-protein-kinase (MAPK) signaling to late endosomes, is critical for the function of neutrophils, B-cells, cytotoxic T-cells and melanocytes. Combining genetic linkage studies and transcriptional profiling analysis, we identified a homozygous point mutation in the 3 UTR of p14 (also known as MAPBPIP), resulting in decreased protein expression. In p14-deficient cells, the distribution of late endosomes was severely perturbed, suggesting a novel role for p14 in endosomal biogenesis. These findings have implications for understanding endosomal membrane dynamics, compartmentalization of cell signal cascades, and their role in immunity.
A novel human primary immunodeficiency syndrome caused by deficiency of the endosomal adaptor protein p14.
Specimen part
View SamplesSulforaphane (SFN), an isothiocyanate, is part of an important group of naturally occurring small molecules with antiinflammatory properties. Even though the published reports are vague, most are best conceivable with an inhibition of T cell functions. We therefore analyzed the effect of SFN on T cell-mediated autoimmune disease. Feeding mice with SFN protected from severe experimental autoimmune encephalomyelitis (EAE). Disease amelioration was associated with reduced interleukin (IL)-17 and IFN-gamma expression in draining lymph nodes. In vitro, SFN treatment of T cells did not directly alter T cell cytokine secretion. In contrast, SFN treatment of dendritic cells (DC) inhibited TLR4-induced IL-12 and IL-23 production and the cytokine profile of T cells stimulated by SFN-treated DC. SFN suppressed TLR4-induced nuclear factor kappa B (NFB) activity, without affecting the degradation of its inhibitor (IB). Instead, SFN treatment of DC resulted in strong expression of the stress response protein heme oxygenase-1 (HO-1), which interacts with NFB p65 and inhibits its activity. Consistent with these findings, HO-1 bound to p65 and subsequently inhibited the p65 promoter activity within the IL23a and IL12b promoter region. Importantly, SFN suppressed Il23a and Il12b expression in vivo and silenced Th17/Th1 responses within the CNS . Our data show that SFN improves Th17/Th1-mediated autoimmune disease by inducing HO-1 and inhibiting p65-regulated IL-23 and IL-12 expression.
Sulforaphane protects from T cell-mediated autoimmune disease by inhibition of IL-23 and IL-12 in dendritic cells.
Specimen part, Treatment
View SamplesTo investigate potential differences between strong and weak oscillators at the gene expression level we carried out a transcriptome analysis for each cell line. Our results indicate that phenotypic circadian clock differences are reflected by gene expression differences both in genes of the core network, but also in additional genes not directly associated with circadian clock functions.
Ras-mediated deregulation of the circadian clock in cancer.
Specimen part, Cell line, Time
View SamplesThe ability to dissect heterogeneity in colorectal cancer (CRC) is a critical step in developing predictive biomarkers. The goal of this study was to develop a gene expression based molecular subgrouping model, which predicts the likelihood that patients will respond to specific therapies.
Activation of the mTOR Pathway by Oxaliplatin in the Treatment of Colorectal Cancer Liver Metastasis.
No sample metadata fields
View SamplesPurpose: Identify differentially expressed genes in placental samples from early-onset (EO) IUGR, EO-PE, as well as pregnancies complicated by both EO-PE and EO-IUGR Overall design: Methods: Isolated total RNA from human placenta at birth and used it for RNA-sequencing on the Hiseq2000. Sequences were aligned to the human transcriptome (hg19/genome_build37) . Aligned sequences were then used to obtain abundance measurements and conduct differential expression analysis.
Placental microRNAs in pregnancies with early onset intrauterine growth restriction and preeclampsia: potential impact on gene expression and pathophysiology.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Alignment of time course gene expression data and the classification of developmentally driven genes with hidden Markov models.
No sample metadata fields
View SamplesWe studied intragraft gene expression profiles of positive crossmatch (+XM) kidney transplant recipients who develop transplant glomerulopathy (TG) and those who do not. Whole genome microarray analysis and quantitative rt-PCR for 30 transcripts were performed on RNA from protocol renal allograft biopsies in 3 groups: 1) +XM/TG+ biopsies before and after TG; 2) +XM/NoTG; and 3) negative crossmatch kidney transplants (control). Microarray comparisons showed few differentially expressed genes between paired biopsies from +XM/TG+ recipients before and after the diagnosis of TG. Comparing +XM/TG+ and control groups, significantly altered expression was seen for 2,447 genes (18%) and 3,200 genes (24%) at early and late time points, respectively. Canonical pathway analyses of differentially expressed genes showed inflammatory genes associated with innate and adaptive immune responses. Comparing +XM/TG+ and +XM/NoTG groups, 3,718 probe sets were differentially expressed but these were over-represented in only 4 pathways. A classic accommodation phenotype was not identified. Using rt-PCR, the expression of inflammatory genes was significantly increased in +XM/TG+ recipients compared to control biopsies and to +XM/NoTG biopsies. In conclusion, pre-transplant DSA results in a gene expression profile characterized by inflammation and cellular infiltration and the majority of XM+ grafts are exposed to chronic injury.
Intragraft gene expression in positive crossmatch kidney allografts: ongoing inflammation mediates chronic antibody-mediated injury.
Specimen part, Time
View SamplesChanges in gene expression during berry development during a grape growing season were analysed.
Alignment of time course gene expression data and the classification of developmentally driven genes with hidden Markov models.
No sample metadata fields
View SamplesDifferences in gene expression were compared for grape berry flesh and skin.
Alignment of time course gene expression data and the classification of developmentally driven genes with hidden Markov models.
No sample metadata fields
View SamplesThe primary aim of this project was to identify novel factors, in particular the cell-surface protein CD109, which regulate osteoclastogenesis. Microarray analysis was performed comparing two pre-osteoclast cell lines generated from the RAW 264.7 osteoclast cell line: one that has the capacity to fuse forming large multinucleated cells and one that does not fuse. It was found that CD109 was up-regulated by > 17-fold in the osteoclast forming cell line when compared to the cell line that does not fuse.
CD109 plays a role in osteoclastogenesis.
Specimen part, Cell line
View Samples