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SRP148791
Mus musculus
17 Downloadable Samples
NextSeq 500
Description
Purpose: Controlling the balance between immunity and immunopathology is crucial for host resistance to pathogens. Upon infection, activation of the hypothalamic-pituitary-adrenal (HPA) axis leads to the production of glucocorticoids (GCs). However, the pleiotropic effects of these steroid hormones make it difficult to decipher their precise role in vivo. Our purpose was to study how GCs regulate the function of group 1 ILCs in spleen and liver upon Murine Cytomegalovirus (MCMV) infection. Methods: We studied the in vivo effect of endogenous GCs released upon MCMV infection on NK cells in spleen and liver and ILC1s in the liver. We compared WT mice with GRNcr1-iCre mice, in which the gene encoding for GC receptor (GR) is selectively deleted in Ncr1+ cells. Results: We found that the regulation of NK function by the GR is required for host protection against MCMV. Mechanistically, endogenous GCs produced shortly after infection induce the selective and tissue-specific expression of the immune checkpoint PD1 on NK cells. This GC-PD1 pathway mediates its immunoregulatory functions by limiting interferon (IFN)-g production by splenic NK cells, preventing lethal immunopathology. Importantly, this regulation does not compromise viral clearance. Conclusions:The fine-tuning of a selective subset of ILCs by the HPA axis preserves tissue integrity without impairing pathogen elimination, revealing a novel aspect of neuro-immune regulation. Overall design: Splenocytes (after NK cell enrichment with the mouse NK Cell Isolation Kit II, Miltenyi Biotec) and liver lymphocytes were pooled from three mice for each genotype. A FACS Aria III (BD Biosciences) was used to sort approximately 5 x 10^5 NK cells from the spleen and liver and 5 x 10^4 liver-resident ILC1s 44h post MCMV infection. We compared gene expression between glucocorticoid receptor (GR)-sufficient and deficient ILCs to identify the genes whose expression is regulated by GCs. Three biological replicates were generated for all samples except for the GRNcr1-iCre liver ILC1s sample (two biological replicates).
Publication Title
Endogenous glucocorticoids control host resistance to viral infection through the tissue-specific regulation of PD-1 expression on NK cells.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A major limitation in the cancer treatment is the ability of cancer cells to become resistant to chemotherapeutic drugs, by multidrug establishment. Here, we evaluate the possibility to utilize MC70, either as ABC transporters inhibitor or as anticancer agent, in monotherapy or in combination with doxorubicin for cancer treatment. The study was carried out in MCF7/ADR and Caco-2, breast and colon cancer cells, respectively. Cell growth and apoptosis were measured by MTT assay and DNA laddering Elisa kit, respectively. Cell cycle perturbation and cellular targets modulation were analyzed by flowcytometry and western blotting, respectively. MC70 was analyzed for its interaction with ABC transporters, MDR-1, BCRP and MRP-1, and for its anticancer activity. In MCF7/ADR, MC70 slight inhibited cell proliferation and strongly enhanced doxorubicin effectiveness; conversely in Caco-2, it inhibited cell growth without affecting doxorubicin efficacy. In addition, it induced apoptosis, canceled in favor of necrosis when it was given in combination with high doses of the anthracycline. Moreover, MC70 inhibited cell migration probably through its residual activity as sigma-1 ligand. Among the hypothesized molecular and cellular mechanisms responsible for all these effects, modulations of cell cycle, of pAkt and of the three MAPKs phosphorylation were evidenced while activity at transcription level was excluded. MC70 can be considered as a potential new anticancer agent with the capability to enhance doxorubicin effectiveness and an interesting role in the treatment of chemotherapy resistant tumors.
Publication Title
MC70 potentiates doxorubicin efficacy in colon and breast cancer in vitro treatment.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Two colon cancer cell lines are under study. SW480 and SW620. The first one is derived from primary cancer, SW620 are from lymphnode metastatic sites. they both comes from the sampe patient. Polisomal RNA fractions from the two isogenic colon cancer cells lines was purified by sucrose gradient and hybridized on affymetrix hgu133a chips. this study is complementary to the series GSE1323 were total RNA was used instead. Comparison between the polysomal fraction chips and the total RNA chips is performed and the analysis proposed in a paper from the authors (at the moment in preparation).
Publication Title
Global alterations in mRNA polysomal recruitment in a cell model of colorectal cancer progression to metastasis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
SW480 and SW620 are colon cancer cells lines derived from a primary tumor and a corresponding metastasis from the same individual. The numbers indicate the three indipendent replicate RNA samples processed. Three different software packages were used in parallel for signal calculation: Affymetrix microarray suite 5.0, DNA-Chip analyzer, and Robust multi-array analyses.
Publication Title
Global alterations in mRNA polysomal recruitment in a cell model of colorectal cancer progression to metastasis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
- Illumina HiSeq 2500
Description
Cortical interneurons display a remarkable diversity in their morphology, physiological properties and connectivity. Elucidating the molecular determinants underlying this heterogeneity is essential for understanding interneuron development and function. We discovered that alternative splicing differentially regulates the integration of somatostatin- and parvalbumin-expressing interneurons into nascent cortical circuits through the cell-type specific tailoring of mRNAs. Specifically, we identified a role for the activity-dependent splicing regulator Rbfox1 in the development of cortical interneuron subtype specific efferent connectivity. Our work demonstrates that Rbfox1 mediates largely non-overlapping alternative splicing programs within two distinct but related classes of interneurons. Overall design: RNA-seq of FACS sorted PV+ and SST+ cortical interneuronals at P8 of wt and conditional Rbfox1 Kos
Publication Title
Rbfox1 Mediates Cell-type-Specific Splicing in Cortical Interneurons.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The pathology of chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and the majority of lung cancers involve the small airway epithelium (SAE), the single continuous layer of cells lining the airways ?6th generations. The basal cells (BC) are the stem/progenitor cells of the SAE, responsible for the differentiation into intermediate cells and ciliated, club and mucous differentiated cells. To facilitate the study of the biology of the human SAE in health and disease, we immortalized and characterized a normal human SAE basal cell line.
Publication Title
Characterization of an immortalized human small airway basal stem/progenitor cell line with airway region-specific differentiation capacity.
Sample Metadata Fields
Sex, Age, Specimen part, Race
View Samples- Homo sapiens
- 202 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 114 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we analyzed larger RO T1D and HC cohorts. In addition, we examined T1D progression by looking at longitudinal, pre-onset and longstanding T1D samples.
Publication Title
Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 49 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we compared the signature found between unrelated healthy controls and non-diabetic cystic fibrosis patients possessing Pseudomonas aeruginosa pulmonary tract infection.
Publication Title
Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we compared the signature found between unrelated healthy controls and patients with bacterial pneumonia.
Publication Title
Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes.
Sample Metadata Fields
No sample metadata fields
View Samples