Influenza A virus has a broad cellular tropism in the respiratory tract. Infected epithelial cells sense the infection and initiate an antiviral response. To define the antiviral response at the earliest stages of infection we used two different single cycle replication reporter viruses. These tools demonstrated heterogeneity in virus replication levels in vivo. Transcriptional profiling demonstrated tiers of interferon stimulated gene responses that were dependent on the magnitude of virus replication. Uninfected cells and cells with blunted replication expressed a distinct and potentially protective ISG signature. Finally, we used these single cycle reporter viruses to determine the antiviral landscape during virus spread, which unveiled disparate protection mediated by IFN. Together these results highlight the complexity of virus-host interactions within the infected lung and suggest that magnitude and round of replication tune the antiviral response. Overall design: Mice were infected with 10^5 pfu of the indicated virus. Lungs from infefected C57BL/6 were taken at 24 hours post infection. Single cell suspensions were sorted for live CD45-CD31- and the indicated virus-driven fluorophore. Cells were FACS sorted directly into cell lysis buffer for RNA extraction. cDNA libraries were prepared using the SMARTer Universal Low Input RNA Kit (Takara Bio). SAmples were then profiled by illumina sequencing
Distinct antiviral signatures revealed by the magnitude and round of influenza virus replication in vivo.
Specimen part, Cell line, Subject
View SamplesImmunosurveillance 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.
T Cells in Nonlymphoid Tissues Give Rise to Lymph-Node-Resident Memory T Cells.
Specimen part
View SamplesVelo-cardio-facial syndrome/DiGeorge syndrome/22q11.2 deletion syndrome (22q11DS) patients have a submucous cleft palate, velo-pharyngeal insufficiency associated with hypernasal speech, facial muscle hypotonia and feeding difficulties. Inactivation of both alleles of mouse Tbx1, encoding a T-box transcription factor, deleted on 22q11.2, results in a cleft palate and a reduction or loss of branchiomeric muscles. To identify genes downstream of Tbx1 for myogenesis, gene profiling was performed on mandibular arches (MdPA1) from Tbx1+/+ and Tbx1-/- mouse embryos.
Tbx1 is required autonomously for cell survival and fate in the pharyngeal core mesoderm to form the muscles of mastication.
Specimen part
View SamplesVelo-cardio-facial syndrome/DiGeorge syndrome/22q11.2 deletion syndrome (22q11DS) patients have a submucous cleft palate, velo-pharyngeal insufficiency associated with hypernasal speech, facial muscle hypotonia and feeding difficulties. Inactivation of both alleles of mouse Tbx1, encoding a T-box transcription factor, deleted on 22q11.2, results in a cleft palate and a reduction or loss of branchiomeric muscles. To identify genes downstream of Tbx1 for myogenesis, gene profiling was performed on mandibular arches (MdPA1) from Tbx1+/+ and Tbx1-/- mouse embryos.
Tbx1 is required autonomously for cell survival and fate in the pharyngeal core mesoderm to form the muscles of mastication.
Specimen part
View SamplesWe assessed the change in hepatic transciptional pattern after treatment with SGLT-2 inhibitors canagliflozin in a mice model of diet-induced obesity.
SGLT2 inhibition reprograms systemic metabolism via FGF21-dependent and -independent mechanisms.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Novel subtype-specific genes identify distinct subpopulations of callosal projection neurons.
Specimen part
View SamplesMyocardial infarction (MI) often results in left ventricular (LV) remodeling followed by heart failure (HF). It is of great clinical importance to understand the molecular mechanisms that trigger transition from compensated LV injury to HF and to identify relevant diagnostic biomarkers. In this study, we performed transcriptional profiling of LVs in rats with a wide range of experimentally induced infarct sizes and of peripheral blood mononuclear cells (PBMCs) in animals that developed HF.
Transcriptional profiling of left ventricle and peripheral blood mononuclear cells in a rat model of postinfarction heart failure.
Specimen part
View Samples3 subtypes of cortical projection neurons were purified by fluorescence-activated cell sorting (FACS) at 4 different stages of development from mouse cortex. A detailed description of the data set is described in Arlotta, P et al (2005) and Molyneaux, BJ et al (2009). The hybridization cocktails used here were originally applied to the Affymetrix mouse 430A arrays and submitted as GEO accession number GSE2039. The same hybridization cocktails were then applied to the Affymetrix mouse 430 2.0 arrays, and those data are contained in this series.
Novel subtype-specific genes identify distinct subpopulations of callosal projection neurons.
Specimen part
View SamplesM cells are the main site of bacterial translocation in the intestine. We used the in vitro M cell model to study the effect of the commensal bacteria; Lactobacillus salivarius, Eschericha coli and Bacteroides fragilis, on M cell gene expression.
Differential intestinal M-cell gene expression response to gut commensals.
Specimen part, Treatment
View SamplesMutations of the transcriptional regulator Mecp2 cause the X-linked autism spectrum disorder Rett syndrome (RTT), and Mecp2 has been implicated in several other neurodevelopmental disorders. To identify potential target genes regulated directly or indirectly by MeCP2, we performed comparative gene expression analysis via oligonucleotide microarrays on Mecp2-/y (Mecp2-null) and wild-type CPN purified via fluorescence-activated cell sorting (FACS).
Reduction of aberrant NF-κB signalling ameliorates Rett syndrome phenotypes in Mecp2-null mice.
Specimen part
View Samples