This SuperSeries is composed of the SubSeries listed below.
Histone Deacetylases 1 and 2 Regulate Microglia Function during Development, Homeostasis, and Neurodegeneration in a Context-Dependent Manner.
Sex, Age, Specimen part, Treatment
View SamplesHdac1 and 2 are important regulators of developmental processes. In this study we created microglia specific compound Hdac1 and Hdac2 knock out mice. Pre-natal ablation of both Hdac1 and 2 from microglia leads to reduced cell number and altered cell morphology. To investigate how Hdac1 and 2 knock out in microglia alters cellular gene expression profile we carried out RNA-seq analysis at different time points. Overall design: We used FACS sorted microglia cells from control and Hdac1/2fl/flCx3cr1Cre (constituitive knockout) or Hdac1/2fl/flCx3cr1CreERT2 (inducible) mice at different time points viz. Embryonic day 16 (E16 - inducible knockout only), Post natal day 0 (P0), 2 and 6 weeks after birth
Histone Deacetylases 1 and 2 Regulate Microglia Function during Development, Homeostasis, and Neurodegeneration in a Context-Dependent Manner.
Age, Treatment, Subject
View SamplesEpigenetic alterations has been implicated in the pathology of several neurodegenerative diseases. To investigate the role of microglial Hdac1 and 2 in the pathogenesis of Alzheimer's disease (AD), we created microglia specific compound Hdac1 and Hdac2 knock out mice in 5X FAD background. Genetic ablation of Hdac1 and 2 from microglia reduced amyloid plaque burden and improved spatial learning and memory function.
Histone Deacetylases 1 and 2 Regulate Microglia Function during Development, Homeostasis, and Neurodegeneration in a Context-Dependent Manner.
Sex, Specimen part
View SamplesRecent studies have shown that tissue macrophages (MF) arise from embryonic progenitors of the yolk sac (YS) and fetal liver and colonize the tissues before birth. Further studies have proposed that developmentally distinct tissue MF can be identified based on the differential expression of F4/80 and CD11b, but whether a characteristic transcriptional profile exists is largely unknown. Here, we established an inducible fate mapping system that facilitated the identification of A2 progenitors of the YS as source of F4/80hi but not CD11bhi MF. Large-scale transcriptional profiling of MF precursors from the YS until adulthood allowed the description of a complex MF pedigree. We further identified a distinct molecular signature of F4/80hi and CD11bhi MF and found that Irf8 was vital for MF maturation and the innate immune response. Our data provide new cellular and molecular insights into the origin and developmental pathways of tissue MF.
Transcriptome-based profiling of yolk sac-derived macrophages reveals a role for Irf8 in macrophage maturation.
Specimen part
View SamplesThe innate immune cell compartment is highly diverse in the healthy central nervous system (CNS) including parenchymal and non-parenchymal macrophages. However, this complexity is increased in inflammatory settings by the recruitment of circulating myeloid cells. It is unclear which disease-specific myeloid subsets exist and what their transcriptional profiles and dynamics during CNS pathology are. By combining deep single-cell transcriptome analysis, fate mapping, in vivo imaging, clonal analysis, and transgenic lines, we comprehensively characterized unappreciated myeloid subsets in several CNS compartments during neuroinflammation. During inflammation, CNS macrophage subsets undergo self-renewal, and random proliferation shifted towards clonal expansion. Finally, functional studies demonstrated that endogenous CNS tissue macrophages are redundant for antigen presentation. Our results highlight myeloid cell diversity and provide insights into the brain's innate immune system. Overall design: CD45+ cells isolated from different CNS compartments (including leptomeninges, perivascular space and parenchyma, and choroid plexus) and Ly6Chigh and Ly6Clow monocytes from blood were FACS-sorted in 384-well plates and used for scRNAseq. All myeloid cells were sorted from C57BL/6N mice with 8-10 weeks of age at naive stage or at different stages of Experimental Autoimmune Encephalomyelitis (preclinical, onset and peak of the disease). Data are representative of 16-18 mice from three independent experiments. mCEL-Seq2 protocol was used for single cell sequencing (Hashimshony et al. 2016, Herman et al. 2018).
Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation.
Age, Specimen part, Disease, Disease stage, Cell line, Subject
View SamplesHost-environment interfaces such as the dermis comprise tissue macrophages as the most abundant resident immune cell type. Diverse tasks, i.e. to resist against invading pathogens, to attract bypassing immune cells from penetrating vessels and to aid tissue development and repair require a dynamic postnatal coordination of tissue macrophages specification. Here, we delineated the postnatal development of dermal macrophages and their differentiation into distinct subsets by adapting single cell transcriptomics, fate-mapping and tissue imaging. We thereby identified a small phenotypically and transcriptionally distinct subset of embryo-derived skin macrophages that was maintained and largely excluded from the overall postnatal exchange by monocytes. These macrophages specifically interacted with dermal sensory nerves, surveilled and trimmed the myelin sheets and regulated axon sprouting after mechanical injury. In summary, our data show long-lasting functional specification of macrophages in the dermis that is driven by step-wise adaptation to guiding structures and ensures codevelopment of ontogenetically distinct cells within the same compartment. Overall design: Single Cell Sequencing was performed on CD45+CD11b+CD64+Lin-(lineage B220, CD3, NK1.1, Siglec-F, Ly6G) CX3CR1 (low, mid, high) macrophage subsets from mouse dermis after enzymatic digestion
A Subset of Skin Macrophages Contributes to the Surveillance and Regeneration of Local Nerves.
Age, Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment.
Sex, Specimen part, Treatment, Time
View SamplesVSV-M2 is recognized by cytosolic RIG-I. Notably, 5'-triphosphate RNA molecules derived from either viral RNA or from the synthetically produced 3pRNA can also induce RIG-I activation. MDA5 stimulation is achieved using complexed poly(I:C), a synthetic analog of viral dsRNA.
Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment.
Sex, Specimen part, Treatment, Time
View SamplesBrain endothelial cells are an essential part of the blood-brain-barrier (BBB) and, as such, are exposed to proinflammatory mediators as well as danger signals during infections. They might function as decisive cells mediating RNA virus- and IFN-mediated sickness behavior.
Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment.
Specimen part, Treatment, Time
View SamplesMicroarray expression profiling was used to identify genes expressed misexpressed in wild-type Arabidopsis seedlings treated with 5-aza-2 deoxyctidine (5AC) or trichostatin A (TSA), and in decrease in dna methylation1 (ddm1) mutant seedlings.
Changes in global gene expression in response to chemical and genetic perturbation of chromatin structure.
Specimen part
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