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Two distinct ontogenies confer heterogeneity to mouse brain microglia

ABSTRACT: Two distinct ontogenies confer heterogeneity to mouse brain microglia

PROVIDER: PRJNA513193 | ENA |

REPOSITORIES: ENA

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Two distinct ontogenies confer heterogeneity to mouse brain microglia

Project description:Hoxb8 mutant mice show compulsive behavior similar to trichotillomania, a human obsessive-compulsive-spectrum disorder. The only Hoxb8 lineage-labeled cells in the brains of mice are microglia, suggesting that defective Hoxb8 microglia caused the disorder. What is the source of the Hoxb8 microglia? It has been posited that all microglia progenitors arise at embryonic day (E) 7.5 during yolk sac hematopoiesis, and colonize the brain at E9.5. In contrast, we show the presence of two microglia subpopulations: canonical, non-Hoxb8 microglia and Hoxb8 microglia. Unlike non- Hoxb8 microglia, Hoxb8 microglia progenitors appear to be generated during the second wave of yolk sac hematopoiesis, then detected in the aorto-gonad-mesonephros (AGM) and fetal liver, where they are greatly expanded, prior to infiltrating the E12.5 brain. Further, we demonstrate that Hoxb8 hematopoietic progenitor cells taken from fetal liver are competent to give rise to microglia in vivo. Although the two microglial subpopulations are very similar molecularly, and in their response to brain injury and participation in synaptic pruning, they show distinct brain distributions which might contribute to pathological specificity. Non-Hoxb8 microglia significantly outnumber Hoxb8 microglia, but they cannot compensate for the loss of Hoxb8 function in Hoxb8 microglia, suggesting further crucial differences between the two subpopulations.

2019-01-07 | GSE124710 | GEO

Two distinct ontogenies confer heterogeneity to mouse brain microglia.

Project description: Not available

| S-EPMC6053660 | biostudies-literature

Heterogeneity of Brain Metastasis-associated Microglia and Macrophages

Project description:Heterogeneity of Brain Metastasis-associated Microglia and Macrophages

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Heterogeneity of Brain Metastasis-associated Microglia and Macrophages

Project description:Brain metastasis (BrM) represents a challenging clinical issue. The most common treatment options are surgery and irradiation. Little is known about the complex cellular and molecular microenvironment of BrM, thus lacking molecular targets to combat this dismal disease. It is known that macrophages from the periphery (monocyte-derived macrophages, MDM) and microglia, the brain-resident macrophages, comprise the most abundant stromal cell types in BrM. However, it is not known if both cell types represent a homogeneous cell population with redundant functions or if there are differences due to their ontologic origin. Besides breast cancer and melanoma, the highest incidence of BrM can be found in lung cancer. To gain deeper insight into the myeloid immune landscape and the heterogeneity of BrM-associated immune cells, we here provide single cell RNA Seq data of microglia and MDMs which were associated with a lung cancer (LuCa) BrM, as well as with an irradiated LuCa BrM. Cells were FACS purified into 384 well plates, snap frozen on dry ice and single cell RNA-Seq performed. Together, our data hint towards cell type-specific heterogeneity both, before and upon application of irradiation.

2020-05-13 | GSE137512 | GEO

Self-renewal of Differentiated Microglia Involves Two Distinct Mechanisms II

Project description:Self-renewal of Differentiated Microglia Involves Two Distinct Mechanisms II

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Single-cell transcriptomics reveals distinct microglia signatures under inflammation

Project description:Microglia are specialized parenchymal-resident phagocytes of the central nervous system (CNS) that actively support, defend and modulate the neural environment. Dysfunctional microglia responses are believed to worsen CNS diseases, nevertheless their impact during the neuroinflammatory processes remains largely obscure. Here, using a combination of multicolor flow cytometry and single-cell RNA sequencing, we comprehensively profiled microglia in the brain of lipopolysaccharide (LPS)-injected mice. By excluding the contribution of other immune CNS-resident and peripheral cells, we showed that microglia isolated from LPS-injected mice displayed a global downregulation of their homeostatic signature together with an upregulation of inflammatory genes. Notably, we identified distinct microglia activated profiles under inflammatory conditions, which greatly differ from neurodegenerative disease-associated profiles. These results provide insights into microglia heterogeneity and establish a resource for the identification of specific phenotypes in CNS disorders, such as neuroinflammatory and neurodegenerative diseases.

2018-09-10 | GSE115571 | GEO

Single-Cell Analysis Uncovers Dramatic Alteration of Microglia Heterogeneity after Ischemic Stroke

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Self-renewal of Differentiated Microglia Involves Two Distinct Mechanisms

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Single cell RNA sequencing reveals functional heterogeneity and sex differences of glioma-associated brain macrophages

Project description:Single cell RNA-seq analysis of CD11b+ cells sorted from murine syngeneic gliomas, indicating distinct activity of microglia, infiltrating monocytes/macrophages and CNS border associated macrophages. It demonstrates a molecular heterogeneity in the innate immune response in gliomas. Differently expressed genes were identified in activated microglia from glioma-bearing mice of different sex, and profound overexpression of the MHCII genes was observed in male microglial cells.

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PSEN1ΔE9, APPswe and APOE4 confer disparate phenotypes in human iPSC-derived microglia

Project description:PSEN1ΔE9, APPswe and APOE4 confer disparate phenotypes in human iPSC-derived microglia

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