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SRP188226
Mus musculus
17 Downloadable Samples
Illumina HiSeq 2500
Description
This study examines the extent to which memory CD4+ T cells share immunosurveillance strategies with CD8+ resident memory T cells (TRM). After acute viral infection, memory CD4+ T cells predominantly utilized residence to survey nonlymphoid tissues, albeit not as stringently as observed for CD8+ T cells. In contrast, memory CD4+ T cells were more likely to be resident within lymphoid organs than CD8+ T cells. Migration properties of memory-phenotype CD4+ T cells in non-SPF parabionts were similar, generalizing these results to diverse infections and conditions. CD4+ and CD8+ TRM shared overlapping transcriptional signatures and location-specific features, such as granzyme B expression in the small intestine, revealing tissue-specific and migration property-specific, in addition to lineage-specific, differentiation programs. Functionally, mucosal CD4+ TRM reactivation locally triggered both chemokine expression and broad immune cell activation. Thus, residence provides a dominant mechanism for regionalizing CD4+ T cell immunity, and location enforces shared transcriptional, phenotypic, and functional properties with CD8+ T cells. Overall design: 17 samples were analyzed by RNA-Sequencing: 3 replicates of resident memory SMARTA CD4 cells (CD62L- CD69+) from the female reproductive tract (FRT) , 2 replicates of resident memory SMARTA CD4 cells (CD62L- CD69+) from the small intestine epithelium (IEL), 3 replicates of resident memory SMARTA CD4 cells (CD62L- CD69+) small intestine lamina propria (LP), 3 replicates of resident memory SMARTA CD4 cells (CD62L- CD69+) from the spleen (SLO), 3 replicates of SMARTA CD4 cells (CD62L+ CD69- or TCM) from the spleen of mice, and 3 replicates of SMARTA CD4 cells (CD62L- CD69- or TEM) from the spleen of mice infected with LCMV-Armstrong 54 days prior.
Publication Title
CD4<sup>+</sup> resident memory T cells dominate immunosurveillance and orchestrate local recall responses.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Immunosurveillance of secondary lymphoid organs (SLO) is performed by central memory T cells that recirculate through blood. Resident memory T cells (TRM) remain parked in nonlymphoid tissues and often stably express CD69. We recently identified TRM within SLO, and this study addresses knowledge gaps in their origin and phenotype. Parabiosis of dirty mice revealed that CD69 expression is insufficient to infer stable residence. Using selective depletion strategies, parabiosis, imaging, tissue grafting, and photoactivatable T cells, we report that restimulation of TRM within the skin or mucosa results in a substantial increase in TRM that patrol all regions of draining lymph nodes. SLO TRM were derived from nonlymphoid tissue residents. Transcriptional profiling and flow cytometry revealed a refined phenotype shared between both nonlymphoid and SLO TRM. These data demonstrate the nonlymphoid origin of SLO TRM and suggest vaccination strategies by which memory CD8 T cell immunosurveillance can be regionalized to specific lymph nodes.
Publication Title
T Cells in Nonlymphoid Tissues Give Rise to Lymph-Node-Resident Memory T Cells.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 21 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
This study investigates the effects of the aryl hydrocarbon receptor (AhR) ligands TCDD, PCB126 and PeCDF; the non-AhR ligand PCB153 and the binary mixture PCB126/PCB153 on hepatic gene expression in female sprague dawley rats. Rats were treated with toxicological equivalent doses of TCDD (100ng/kg), PeCDF (200ng/kg), PCB126 (1000ng/kg) and PCB153 (1000ug/kg) 5 days a week for 13 weeks.
Publication Title
Hepatic gene downregulation following acute and subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Rattus norvegicus
- 15 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
This study investigates the effects of the aryl hydrocarbon receptor (AhR) ligands TCDD and PCB126 on hepatic gene expression in female sprague dawley rats. Rats were treated with toxicological equivalent doses of TCDD (100ng/kg/day) (Toxic equivalence factor (TEF) = 1.0), PCB126 (30ng, 300ng or 1000ng/kg/day) (TEF = 0.1) or a vehicle control of corn oil:acetone (99:1) 5 days a week for 52 weeks.
Publication Title
Toxicogenomic analysis of exposure to TCDD, PCB126 and PCB153: identification of genomic biomarkers of exposure to AhR ligands.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This study presents transcription profiles for mouse axial progenitors, presomitic mesoderm and tailbud mesoderm. During vertebrate embryonic development, the formation of axial structures is driven by a population of stem-like cells (axial progenitors) that reside in a region of the tailbud called the chordoneural hinge (CNH) where. We have compared the CNH transcriptome with those of surrounding tissues and shown that the CNH and tailbud mesoderm are transcriptionally similar, and distinct from the presomitic mesoderm. Amongst CNH-enriched genes are several that are required for axial elongation, including Wnt3a, Cdx2, Brachyury/T and Fgf8, and androgen/estrogen receptor nuclear signalling components such as Greb1.
Publication Title
<i>Greb1</i> is required for axial elongation and segmentation in vertebrate embryos.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 56 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To identify genes implicated in metastatic colonization of the liver in colorectal cancer, we collected pairs of primary tumors and hepatic metastases before chemotherapy in 13 patients. We compared mRNA expression in the pairs of patients to identify genes deregulated during metastatic evolution. We then validated the identified genes using data obtained by different groups. The 33-gene signature was able to classify 87% of hepatic metastases, 98% of primary tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six datasets obtained using five different microarray platforms. The identified genes are specific to colon cancer and hepatic metastases since other metastatic locations and hepatic metastases originating from breast cancer were not classified by the signature. Gene Ontology term analysis showed that 50% of the genes are implicated in extracellular matrix remodeling, and more precisely in cell adhesion, extracellular matrix organization and angiogenesis. Because of the high efficiency of the signature to classify colon hepatic metastases, the identified genes represent promising targets to develop new therapies that will specifically affect hepatic metastasis microenvironment.
Publication Title
Specific extracellular matrix remodeling signature of colon hepatic metastases.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 426 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The aim of the present study was to characterize the gene expression profile of the phosphodiesterase-4 inhibitor CHF6001 on top of inhaled triple therapy in sputum cells and whole blood of chronic bronchitis patients. Samples for analyses were collected from a multicenter, three-period, three-way, placebo-controlled, double-blind, complete block crossover study. Eligible patients underwent three, 32-day treatment periods during which they received CHF6001 800 or 1600 µg twice daily (total daily doses of 1600 or 3200 µg) or matching placebo, all via multi-dose dry-powder inhaler (NEXThaler). Treatment periods were separated by a 28–42 day washout. Eligible patients were male or female, ≥40 years of age, current or ex-smokers with a smoking history ≥10 pack-years, a diagnosis of COPD, post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥30% and <70% predicted, ratio of FEV1 to forced vital capacity (FVC) <0.70, COPD Assessment Test score ≥10, and a history of chronic bronchitis (defined as chronic cough and sputum production for more than three months per year for at least two years) and treated with inhaled triple ICS/LABA/LAMA therapy for at least two months prior to enrollment. CHF6001 had no effect in blood, but a strong effect in sputum with 1471 and 2598 significantly differentially-expressed probe-sets relative to placebo (p-value adjusted for False Discovery Rate<0.05) for 800 and 1600µg , respectively. Functional enrichment analysis showed significant modulation of key inflammatory pathways involved in cytokine activity, pathogen-associated-pattern-recognition activity, oxidative stress and vitamin D with associated inhibition of downstream inflammatory effectors. A large number of pro-inflammatory genes coding for cytokines and matrix-metalloproteinases were significantly differentially expressed for both doses; the majority (>87%) were downregulated, including macrophage inflammatory protein-1-alpha and 1-beta, interleukin-27-beta, interleukin-12-beta, interleukin-32, tumor necrosis factor-alpha-induced-protein-8, ligand-superfamily-member-15, and matrix-metalloproteinases-7,12 and 14. In conclusion inhaled PDE4-Inhibition by CHF6001 on top of triple therapy in patients with chronic bronchitis patients significantly modulated key inflammatory targets and pathways in the lung but not in blood. Mechanistically these findings support a targeted effect in the lung while minimizing unwanted systemic class-effects
Publication Title
Sputum and blood transcriptomics characterisation of the inhaled PDE4 inhibitor CHF6001 on top of triple therapy in patients with chronic bronchitis.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples