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GSE11818
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A new Treg-specific, FoxP3-GFP-hCre BAC transgenic was crossed to a conditional Dicer knock-out mouse strain to analyze the role of microRNAs (miRNA) in the development and function of regulatory T cells (Tregs). Although thymic Tregs developed normally in this setting, the cells showed evidence of altered differentiation and dysfunction in the periphery. Dicer-deficient Treg lineage cells failed to remain stable as a subset of cells down-regulated the Treg-specific transcription factor, FoxP3, while the majority expressed altered levels of multiple genes and proteins (including Neuropilin 1, GITR and CTLA-4) associated with the Treg fingerprint. In fact, a significant percentage of the Treg lineage cells took on a Th memory phenotype including increased levels of CD127, IL-4, and interferon-g. Importantly, Dicer-deficient Tregs lost suppression activity in vivo; the mice rapidly developed fatal systemic autoimmune disease resembling the FoxP3 knockout phenotype. These results support a central role for miRNAs in maintaining the stability of differentiated Treg function in vivo and homeostasis of the adaptive immune system.
Publication Title
Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Regulatory T cells (Treg) are pivotal for the maintenance of peripheral tolerance by controlling self-reactive, chronic and homeostatic T cell responses. We now report that the increase in Treg suppressive function observed in lymphopenic mice correlates with the degree of lymphopenia and is caused by a higher frequency of a novel subpopulation of CD103posICOSpos cells among peripheral Treg that differentially express multiple Treg signature genes.
Publication Title
A subpopulation of CD103(pos) ICOS(pos) Treg cells occurs at high frequency in lymphopenic mice and represents a lymph node specific differentiation stage.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
Illumina HiSeq 2500
Description
MicroRNAs (miRNAs) are important regulators of cell fate decisions in immune responses. They act by coordinate repression of multiple target genes, a property that we exploited to uncover regulatory networks that govern T helper-2 (Th2) cells. A functional screen of individual miRNAs in primary T cells uncovered multiple miRNAs that inhibited Th2 cell differentiation. Among these were miR-24 and miR-27, miRNAs coexpressed from two genomic clusters, which each functioned independently to limit interleukin-4 (IL-4) production. Mice lacking both clusters in T cells displayed increased Th2 cell responses and tissue pathology in a mouse model of asthma. Gene expression and pathway analyses placed miR-27 upstream of genes known to regulate Th2 cells. They also identified targets not previously associated with Th2 cell biology which regulated IL-4 production in unbiased functional testing. Thus, elucidating the biological function and target repertoire of miR-24 and miR-27 reveals regulators of Th2 cell biology. Overall design: Gene expression analysis of miRNA-deficient mouse CD4+ T cells transfected with miRNA mimics twice over a 5 day in vitro culture in the presence of low amounts of exogenous IL-4 (10U/ml). Cells transfected with either miR-23, miR-24 or miR-27 were compared to cells transfected with a control mimic. Data are from at least biologic triplicates.
Publication Title
MicroRNAs 24 and 27 Suppress Allergic Inflammation and Target a Network of Regulators of T Helper 2 Cell-Associated Cytokine Production.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Ion Torrent Proton
Description
We report, for the first time, engineering of heteropolar cardiac tissues containing distinct atrial and ventricular ends, and demonstrate their spatially confined responses to serotonin and ranolazine. Uniquely, electrical conditioning for up to 8 months enabled modeling of polygenic left ventricular hypertrophy starting from patient cells. Overall design: hiPSC-CMs from 3 affected (Left Ventricular Hypertrophy [LVH]) and 3 non-affected donors were sequenced using ThermoFisher's whole transcriptome targeted AmpliSeq assay
Publication Title
A Platform for Generation of Chamber-Specific Cardiac Tissues and Disease Modeling.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples