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GSE70475
Mus musculus
18 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Microglia are phagocytic cells that survey the brain and perform neuroprotective functions in response to tissue damage, but their activating receptors are largely unknown. Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial immunoreceptor whose loss-of-function mutations in humans cause presenile dementia, while genetic variants are associated with increased risk of neurodegenerative diseases. In myeloid cells, TREM2 has been involved in the regulation of phagocytosis, cell proliferation and inflammatory responses in vitro. However, it is unknown how TREM2 contributes to microglia function in vivo. Here, we identify a critical role for TREM2 in the activation and function of microglia during cuprizone (CPZ)-induced demyelination. TREM2-deficient (TREM2(-/-)) mice had defective clearance of myelin debris and more axonal pathology, resulting in impaired clinical performances compared to wild-type (WT) mice. TREM2(-/-) microglia proliferated less in areas of demyelination and were less activated, displaying a more resting morphology and decreased expression of the activation markers MHC II and inducible nitric oxide synthase as compared to WT. Mechanistically, gene expression and ultrastructural analysis of microglia suggested a defect in myelin degradation and phagosome processing during CPZ intoxication in TREM2(-/-) microglia. These findings place TREM2 as a key regulator of microglia activation in vivo in response to tissue damage.
Publication Title
TREM2 regulates microglial cell activation in response to demyelination in vivo.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 647 Downloadable Samples
Description
We adopted the STRT-seq [Islam et al., Nat Methods 11, 163-166 (2013)] RNA-seq technology to a 9600-well array and applied it to analyze single cells from mouse and human cortex single cells. Overall design: 2192 single cells from mouse somatosensory cortex and 2028 single nuclei from human post-mortem middle temporal gyrus cortex.
Publication Title
STRT-seq-2i: dual-index 5' single cell and nucleus RNA-seq on an addressable microwell array.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Breast cancer metastasis to bone is a critical determinant of long-term survival after treatment of primary tumors. We used a mouse model of spontaneous bone metastasis to determine new molecular mechanisms. Differential transcriptome comparisons of primary and metastatic tumor cells revealed that a substantial set of genes suppressed in bone metastases were highly enriched for promoter elements for the type I interferon (IFN) regulatory factor, Irf7, itself suppressed in mouse and human metastases. The critical function of the Irf7 pathway was demonstrated by restoration of exogenous Irf7 or systemic interferon administration, which significantly reduced bone metastases and prolonged metastasis-free survival. Using mice deficient in the type I receptor (Ifnar1-/-) or mature B, T and NK cell responses (NOD Scid IL-2r-/- mice), we demonstrated that Irf7-driven suppression of metastasis was reliant on IFN signaling to host immune cells. Metastasis suppression correlated with decreased accumulation of myeloid-derived suppressor cells and increased CD4++, CD8 T cells and NK cells in the peripheral blood and was reversed by depletion of CD8+ cells and NK cells. Clinical importance of our findings was demonstrated as increased primary tumor Irf7 expression predicted prolonged bone and lung metastasis-free survival. Thus we report for the first time, a novel innate immune pathway, intrinsic to breast cancer cells, whose suppression in turn restricts systemic immunosurveillance to enable metastasis. This pathway may constitute a novel therapeutic target for restricting breast cancer metastases.
Publication Title
Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 42 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
BALB/c mice are susceptible to proteoglycan (PG) aggrecan-induced arthritis (PGIA), and the absence of TSG-6 further increases susceptibility and local inflammatory reactions, including neutrophil invasion into the joints. To gain insight into the mechanisms of TSG-6 action, synovial fibroblasts were isolated from wild-type and TSG-6-KO mice, cultured and exposed to various agents affecting either the TSG-6 expression and/or modify the intracellular function of TSG-6.
Publication Title
TSG-6 protein, a negative regulator of inflammatory arthritis, forms a ternary complex with murine mast cell tryptases and heparin.
Sample Metadata Fields
Sex, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
BALB/c mice are susceptible to proteoglycan (PG) aggrecan-induced arthritis (PGIA), a murine model of rheumatoid arthritis (Glant,T.T. and Mikecz,K., Proteoglycan aggrecan-induced arthritis. A murine autoimmune model of rheumatoid arthritis. Methods Mol.Med. 2004. 102: 313-338.). However, there are marked differences among BALB/c colonies (maintained by different vendors at different locations) in PGIA onset and severity, which could be the result of subtle variations in their genetic background.
Publication Title
BALB/c mice genetically susceptible to proteoglycan-induced arthritis and spondylitis show colony-dependent differences in disease penetrance.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 23 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose:Next-generation sequencing has revolutionized sytems-level celluar pathway analysis. The goals of this study are to compare the U87 cell xenograft GBM mice (U87 cell line) to TWIST1 knock out U87 cell xenograft GBM mice (TWIST1 knock out U87 cell line) using their transcriptomes Overall design: Methods: Investigation of TWIST1 expression on glioblastoma malignancy in vitro and in vivo.
Publication Title
Targeting TWIST1 through loss of function inhibits tumorigenicity of human glioblastoma.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
An Ancient Fecundability-Associated Polymorphism Creates a GATA2 Binding Site in a Distal Enhancer of HLA-F.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
This study aims to demonstrate the link between epigenome-wide methylation aberrations at birth and genomic transcriptional changes upon allergen sensitization that occur in the neonatal dendritic cells (DC) due to maternal asthma. In an in vivo model reproducing human epidemiology findings, maternal but not paternal asthma predisposes the neonate to increased asthma risk, the effect is allergen-independent and is not genetic or environmental. Earlier we demonstrated that neonates of asthmatic mothers are born with a functional skew in splenic DCs that mediates the early-life asthma origin. These allergen-naive cells convey allergy responses to normal recipients, however minimal to no transcriptional or phenotypic changes were found to explain the functional pro-allergic alterations. In this study we profiled both allergen-nave dendritic cells, and cells after allergen sensitization in vivo. We found that while allergen-naive DCs from asthma-at-risk neonates have minimal transcriptional change compared to controls, upon allergen sensitization, multiple genes with pre-existing epigenetic alterations show significant transcriptional change. .
Publication Title
Link between epigenomic alterations and genome-wide aberrant transcriptional response to allergen in dendritic cells conveying maternal asthma risk.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Caenorhabditis elegans
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
XRN2 is a conserved 5’-->3’ exoribonuclease that complexes with XTB-domain containing proteins. Thus, in Caenorhabditis elegans (C. elegans), the XTBD-protein PAXT-1 stabilizes XRN2 to retain its activity. XRN2 activity is also promoted by 3''(2''),5''-bisphosphate nucleotidase 1 (BPNT1) through its hydrolysis of 3’-phosphoadenosine-5''-bisphosphate (PAP), an endogenous XRN inhibitor. Here, we find through unbiased screening that loss of bpnt-1 function suppresses lethality caused by paxt-1 deletion. This unexpected finding is explained by XRN2 autoregulation, which occurs through repression of a cryptic promoter activity and destabilization of the xrn-2 transcript. Autoregulation appears to be triggered at different thresholds of XRN2 inactivation, such that more robust XRN2 perturbation, by elimination of both PAXT-1 and BPNT1, is less detrimental to worm viability than absence of PAXT-1 alone. Like more than 15% of C. elegans genes, xrn-2 occurs in an operon, and we identify additional operons under its control, consistent with a broader function of XRN2 in polycistronic gene regulation. Regulation occurs through intercistronic regions that link genes in an operon, but similar mechanisms may allow XRN2 to operate on monocistronic genes in organisms lacking operons. Overall design: Wild-type C. elegans worms were subjected to mock or xrn-2 RNAi from L1 to L4 stage at 20°C. Total RNA was extracted from the worms, and polyadenylated RNA was analyzed.
Publication Title
XRN2 Autoregulation and Control of Polycistronic Gene Expresssion in Caenorhabditis elegans.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The goal is to investigate gene regulation in endometrial stromal cells expressing the Notch ligand Jag1.
Publication Title
Notch ligand-dependent gene expression in human endometrial stromal cells.
Sample Metadata Fields
Specimen part
View Samples