Filters
Technology
Platform
SRP043144
Homo sapiens
12 Downloadable Samples
IlluminaHiSeq2500
Description
SAMHD1 restricts HIV-1 replication in dendritic and other myeloid cells. SAMHD1 has been shown to possess a dGTP-dependent dNTP triphosphatase (dNTPase) activity and is proposed to inhibit HIV-1 replication by depleting the intracellular dNTP pool. Arguing against a role for SAMHD1 dNTPase in HIV-1 restriction, the phosphorylation of SAMHD1 regulates the restriction activity toward HIV-1 without affecting its ability to decrease cellular dNTP levels. Here, we show that SAMHD1 is a phospho-regulated RNase and that the RNase function is required for HIV-1 restriction. Mutation of the SAMHD1 D137 residue in the allosteric site (SAMHD1D137N) abolishes dNTPase activity but has no effect on RNase activity. This dNTPase-defective SAMHD1D137N mutant is able to restrict HIV-1 infection to nearly the same extent as wild-type SAMHD1. SAMHD1 associates with and degrades the HIV-1 genomic RNA during the early phases of infection. SAMHD1 silencing in macrophages and CD4+ T cells from healthy donors increases HIV-1 RNA stability, thus rendering the cells permissive for HIV-1 infection. Furthermore, the phosphorylation of SAMHD1 at position T592 abolishes the RNase activity toward HIV-1 RNA, and consequently the ability of SAMHD1 to restrict HIV-1 infection, uncovering the phosphorylation of SAMHD1 T592 as a negative regulatory mechanism of RNase activity. Together, our results demonstrate that SAMHD1 is an essential RNase that prevents HIV-1 infection by directly degrading HIV-1 genomic RNA in a phosphorylation-regulated manner. The unique property of SAMHD1 that cleaves HIV-1 genomic RNA with no sequence preferences could be exploited to develop a new class of intervention for error-prone retroviruses. Overall design: Ribosomal RNA-depleted total RNA profiles of mock, SAMHD1 wild type and mutants infected with HIV-1 were examined at the time of 0, 1, 3 h by Illumina Hiseq2500.
Publication Title
The ribonuclease activity of SAMHD1 is required for HIV-1 restriction.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: The goal of the study was to integrate verified signals from previous genetic association studies with gene expression and pathway analysis for discovery of new candidate genes and signalling networks, relevant for rheumatoid arthritis (RA). Method:RNA-seq based expression analysis of 377 genes from previously verified RA-associated loci was performed in blood cells from 5 newly diagnosed, non-treated RA patients, 7 patients with treated RA and 12 healthy controls. Differentially expressed genes sharing a similar expression pattern in treated and untreated RA sub-groups were selected for pathway analysis. A set of “connector” genes derived from pathway analysis was then tested for differential expression in the initial discovery cohort. Results: 11 qualifying genes were selected for pathway analysis and grouped into 2 evidence-based functional networks, containing 29 and 27 additional “connector” molecules. The expression of genes, corresponding to connector molecules was then tested in the initial RNA-seq data. 3 genes showed similar expression difference in both treated and non-treated RA patients and additional nine genes were differentially expressed in at least one patients' group compared to healthy controls. Conclusion: Integration of RNA-seq data with findings from association studies, and consequent pathway analysis implicate new candidate genes in the pathogenesis of RA. Overall design: Illumina RNA-seq was performed on RNA from pereferial blood mononuclear cells taken from 12 healthy individuals, 5 untreated RA patients, and 7 treated RA patients
Publication Title
Discovery of new candidate genes for rheumatoid arthritis through integration of genetic association data with expression pathway analysis.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 32 Downloadable Samples
- Illumina HiSeq 2500
Description
The presence of the PTPN22 risk variant (1858T) is associated to several autoimmune diseases including rheumatoid arthritis (RA). Despite a number of studies exploring the function of PTPN22 in T cells, the exact impact of the PTPN22 risk variant on T cell function in humans is still unclear. In this study, using RNA sequencing, we show that, upon TCR-activation, naïve CD4+ T cells carrying two PTPN22 risk alleles overexpress a limited number of genes including CFLAR and 4-1BB important for cytotoxic T cell differentiation. Moreover, an increased number of cytotoxic EOMES+ CD4+ T cells were observed in PTPN22 risk allele carriers, which negatively correlated with a decreased number of naïve T cells in older individuals. No difference in the frequency of other CD4+ T cell subsets (Th1, Th17, Tfh, Treg) was observed in PTPN22 risk allele carriers and Treg suppressive capacity was not altered. Finally, in synovial fluids of RA patients, an accumulation of EOMES+ CD4+ T cells was observed with a more pronounced production of Perforin-1 in PTPN22 risk allele carriers. Altogether, our data provide a novel mechanism of action of PTPN22 risk variant on CD4+ T-cell differentiation and identify EOMES+ CD4+ T cell as a relevant T cell subset in RA. Overall design: Healthy blood donors were selected based PTPN22 genotype, and RNA-sequencing was done on CD4 T cells
Publication Title
EOMES-positive CD4<sup>+</sup> T cells are increased in PTPN22 (1858T) risk allele carriers.
Sample Metadata Fields
Sex, Age, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st), Agilent-026652 Whole Human Genome Microarray 4x44K v2 (Probe Name version)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
In preeclampsia (PE), cytotrophoblast (CTB) invasion of the uterus and spiral arteries is often shallow. Thus, the placentas role has been a focus. We hypothesized that decidual defects are an important determinant of the placental phenotype. We isolated (human) endometrial stromal cells (hESCs) from non-pregnant donors with a prior pregnancy that was complicated by severe PE (sPE). Versus controls, they failed to decidualize as demonstrated by morphological criteria and the analysis of stage-specific antigens. These results were bolstered by showing that they were transcriptionally inert. Additionally, we used laser microdissection to isolate the decidua from tissue sections of the maternal-fetal interface. Transcriptional profiling revealed sPE-associated defects in gene expression. Also, decidual cells from sPE patients, which de-differentiated in vitro, failed to re-decidualize in culture. Immediately following isolation they released factors that inhibited CTB invasion, linking a possible cause to a known effect. These data suggested that failed decidualization is an important contributor to down regulated CTB invasion in sPE. Diagnosis of this defect prior to pregnancy would enable therapies that are designed to improve decidualization, a novel strategy for prevention.
Publication Title
Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA-binding proteins (RBPs) facilitate post-transcriptional control of eukaryotic gene expression at multiple levels. The RBP tristetraprolin (TTP/Zfp36) is a signal-induced phosphorylated anti-inflammatory protein guiding unstable mRNAs of pro-inflammatory proteins for degradation and preventing translation. Using iCLIP, we have identified numerous mRNA targets bound by wild-type TTP and by a non-MK2-phosphorylatable TTP mutant (TTP-AA) in 1h LPS-stimulated macrophages and correlated their interaction with TTP to changes at the level of mRNA abundance and translation in a transcriptome-wide manner. The close similarity of the transcriptome of TTP-deficient and TTP-expressing macrophages upon short LPS stimulation suggested an effective inactivation of TTP by MK2 under these conditions whereas retained RNA-binding capacity of TTP-AA to 3’UTRs caused profound changes in the transcriptome and translatome, altered NF-?B-activation and induced cell death. Increased TTP binding to the 3''UTR of feedback inhibitor mRNAs, such as Ier3, Dusp1 or Tnfaip3, in the absence of MK2-dependent TTP neutralization resulted in a strong reduction of their protein synthesis contributing to the deregulation of the NF-?B-signaling pathway. Taken together, our study uncovers a role for TTP in NF-?B-signaling and highlights the importance of fine-tuned TTP activity-regulation by MK2 in order to control feedback signaling during the inflammatory response. Overall design: Comparison of the transcriptomes of TTP knockout macrophages inducibly expressing GFP, GFP-TTP or GFP-TTP-AA (S52A, S178A) phosphorylation mutant during 1h LPS stimulation. 3 biological replicates per genotype and condition.
Publication Title
The RNA-binding protein TTP is a global post-transcriptional regulator of feedback control in inflammation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We performed gene expression profiling on in vitro derived PGCs, undifferentiated ESCs, and somatic cells from the EB to examine germ cell expression in ESC-derived cells
Publication Title
Single cell analysis facilitates staging of Blimp1-dependent primordial germ cells derived from mouse embryonic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Background
Publication Title
Gene expression profile of cervical and skin tissues from human papillomavirus type 16 E6 transgenic mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The tumor microenvironment plays a critical role in cancer progression, but the precise mechanisms by which stromal cells influence the tumor epithelium are poorly understood. The signaling adapter p62 has been implicated as a positive regulator of epithelial tumorigenesis; however, its role in the stroma is unknown. We show here that p62 levels are reduced in the stroma of several tumors. Also, orthotopic and organotypic studies demonstrate that the loss of p62 in the tumor microenvironment or stromal fibroblasts resulted in increased tumorigenesis of epithelial prostate cancer cells. The mechanism involves the regulation of cellular redox through an mTORC1/c-Myc pathway of stromal glucose and amino acid metabolism. Inhibition of the pathway by p62 deficiency results in increased stromal IL-6 production, which is required for tumor promotion in the epithelial compartment. Thus, p62 is an anti-inflammatory tumor suppressor that acts through modulation of metabolism in the tumor stroma.
Publication Title
Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
In order to gain insight into the molecular pathogenesis of collagen VI defects we have performed gene expression microarray analysis of dermal fibroblasts. We have compared the transcriptome of fibroblasts, treated or untreated with ascorbic acid, from UCMD patients (n = 6) and aged-matched healthy children (n = 5).
Publication Title
Transcriptome Analysis of Ullrich Congenital Muscular Dystrophy Fibroblasts Reveals a Disease Extracellular Matrix Signature and Key Molecular Regulators.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples