This SuperSeries is composed of the SubSeries listed below.
Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation.
Time
View SamplesGene expression profiling was performed to identify Sfmbt1-dependent regulation in myogenic programs. To establish the magnitude of the Sfmbt1 effect on muscle cells, we have compared gene expression profiles of C2C12 cells transduced with lentiviruses expressing scramble shRNA control or shSfmbt1. Our analysis suggested that Sfmbt1 critically confers transcriptional silencing of muscle genes in myogenic progenitor cells.
Proteomic and functional analyses reveal the role of chromatin reader SFMBT1 in regulating epigenetic silencing and the myogenic gene program.
Specimen part, Cell line
View SamplesWe used microarrays to detail the role of Polycomb proteins including Ezh2 and Eed in maintaining ES cell identity and executing pluripotency.
EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency.
No sample metadata fields
View SamplesCD8 T cells play a crucial role in immunity to infection and cancer. They are maintained in constant numbers, but upon stimulation with antigen undergo a developmental program characterized by distinct phases encompassing the expansion and then contraction of antigen-specific populations, followed by the persistence of long-lived memory cells. Although this predictable pattern of a CD8 T cell response is well established, the underlying cellular mechanisms regulating the transition to memory remain undefined. Here we show that TRAF6, an adapter protein in the TNF-receptor (TNFR) and IL-1R/TLR superfamily, regulates CD8 T cell memory development following infection by modulating fatty acid metabolism. We show that mice with a T cell-specific deletion of TRAF6 mount robust primary CD8 T cell effector responses, but have a profound defect in their ability to generate memory. This defect is CD8 T cell intrinsic and is characterized by the disappearance of antigen-specific cells in the weeks following primary immunization. Microarray analyses revealed that TRAF6-deficient CD8 T cells from early timepoints following immunization exhibit altered expression of genes that regulate fatty acid metabolism. Consistent with this, activated CD8 T cells lacking TRAF6 are unable to upregulate mitochondrial -oxidation in response to growth factor withdrawal in vitro. Treatment with drugs that induce fatty acid oxidation enabled CD8 T cell memory generation in the absence of TRAF6. Remarkably, these treatments also increased CD8 T cell memory in wild type mice, and consequently were able to significantly improve the efficacy of an experimental anti-cancer vaccine.
Enhancing CD8 T-cell memory by modulating fatty acid metabolism.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Jumonji modulates polycomb activity and self-renewal versus differentiation of stem cells.
Specimen part
View SamplesWe used microarrays to detail the role of JMJ in ES cell function.
Jumonji modulates polycomb activity and self-renewal versus differentiation of stem cells.
Specimen part
View SamplesWnt-4 signaling is critical for embryonic female sexual development. When Wnt-4 gene is deleted during embryonic development, the knock-out females present a partial sex reversal.
Identification of the genes regulated by Wnt-4, a critical signal for commitment of the ovary.
Specimen part
View SamplesGroup-2 innate lymphoid cells (ILC2) serve crucial function in allergy and asthma. Activated ILC2 rapidly proliferate and secret large amounts of type-2 cytokines, such as IL-5 and IL-13. Mechanisms underlying still remain ambiguous. Here we report that Myc is required for ILC2 proliferation and activation in allergic airway inflammation. Inhibition of Myc impair the ILC2 proliferation in vivo and prevented ILC2-mediated airway hyperresponsiveness in vivo.
A critical role for c-Myc in group 2 innate lymphoid cell activation.
Genotype, Cell line
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 SamplesPolycomb group (PcG) proteins are epigenetic silencers whose dysregulation is frequently linked to cancer via mechanisms that remain unclear. Using conditional knock-out mice in a colitis-associated colorectal cancer (CAC) model, we found that Bmi1 and Mel18 are important initiation and maintenance factors during CAC tumorigenesis. Epithelial depletion of both Bmi1 and Mel18, but not either gene alone, significantly reduces tumor growth and multiplicity.
BMI1 and MEL18 Promote Colitis-Associated Cancer in Mice via REG3B and STAT3.
Specimen part
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