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Mus musculus
8 Downloadable Samples
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
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
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
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GSE12637- Mus musculus
- 2 Downloadable Samples
Description
This experiment is to identify genes that are regulated by pRb in AC61 cells. AC61 cells were derived from a C-cell adenocarcinoma developed in an Rb+/-N-ras-/- mouse.
Publication Title
Rb Regulates DNA damage response and cellular senescence through E2F-dependent suppression of N-ras isoprenylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 32 Downloadable Samples
Description
Expression profiles generated during dissection of the molecular mechanisms underlying direct reprogramming of somatic cells to a pluripotent state (induced pluripotent stem cells, iPS).
Publication Title
Dissecting direct reprogramming through integrative genomic analysis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 1 Downloadable Sample
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 1 Downloadable Sample
Description
Differences in the amount of fetal hemoglobin (HbF) that persists into adulthood affect the severity of sickle cell disease and the beta-thalassemia syndromes. Genetic association studies have identified sequence variants in the gene BCL11A that influence HbF levels. Here we examine BCL11A as a potential regulator of HbF expression. The high HbF BCL11A genotype is associated with reduced BCL11A expression. Moreover, abundant expression of full-length forms of BCL11A is developmentally restricted to adult erythroid cells. Down-regulation of BCL11A expression in primary adult erythroid cells leads to robust HbF expression. Consistent with a direct role of BCL11A in globin gene regulation, we find that BCL11A occupies several discrete sites in the beta-globin gene cluster. BCL11A emerges as a therapeutic target for reactivation of HbF in beta-hemoglobin disorders.
Publication Title
Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Comparative analysis of gene expression in cultured primary keratinocytes isolated from newborn control (K14-cre; GPx4fl/+) and knockout (K14-cre; GPx4fl/fl) mice.
Publication Title
Targeted disruption of glutathione peroxidase 4 in mouse skin epithelial cells impairs postnatal hair follicle morphogenesis that is partially rescued through inhibition of COX-2.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
In vivo mapping of notch pathway activity in normal and stress hematopoiesis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Notch signaling defines a conserved, fundamental pathway, responsible for determination in metazoan development and is widely recognized as an essential component of lineage specific differentiation and stem cell self-renewal in many tissues including the hematopoietic system. Until recently, the majority of studies in the hematopoietic system focused on Notch signaling in lymphocyte differentiation and knowledge of individual Notch receptor roles in early hematopoiesis has been limited due to a paucity of genetic tools available To fate-map Notch receptor expression and pathway activity in the hematopoietic system we used tamoxifen-inducible CreER knock-in mice for individual Notch receptors in combination to a novel Notch reporter strain (Hes1GFP) and a conditional gain of function allele of Notch2 receptor (Rosa-lsl-ICN2).
Publication Title
In vivo mapping of notch pathway activity in normal and stress hematopoiesis.
Sample Metadata Fields
Sex, Age, Specimen part
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