Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Microglia self-renewal comprises context-dependent random or clonal expansion.

ABSTRACT: Microglia constitute a highly specialized network of tissue resident immune cells that is important for the control of tissue homeostasis and the resolution of virtually all diseases of the central nervous system (CNS). However, how this dissemination is established and maintained in vivo and its kinetics of these processes are poorly understood. Here we established a new multicolor fluorescence fate mapping system to monitor microglia dynamics during steady state and disease. Our findings that microglia establish a stable network over time albeit with regional differences and remarkably high turnover rates challenge their postulated longevity. Microglia self-renewal constitutes a random process without evidence of defined progenitor cells. Under pathological conditions this randomness shifts to clonal microglia expansion that is finally resolved by both cell apoptosis and egression for re-establishment of the stable microglia network. Our data reveal new insights on how microglia ensure their complex distribution throughout the healthy and diseased CNS .

ORGANISM(S): Mus musculus

PROVIDER: GSE79252 | GEO | 2017/03/27

SECONDARY ACCESSION(S): PRJNA315281

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

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

RNA sequencing of microglia sorted form tamoxifen treated Sall1CreER/fl and control Sall1fl/fl mice

Project description:Microglia are the resident macrophages of the central nervous system (CNS). Gene profiling identified the transcriptional regulator Sall1 as a microglia signature gene. Given the high expression of Sall1 in microglia, we sought to identify its function in vivo. The Sall1CreER allele has been targeted into the Sall1 locus, therefore Sall1CreER/fl mice (heterozygous for both alleles) allow inducible ablation of Sall1 expression in microglia after tamoxifen treatment. We performed RNA-seq to examine gene expression profiles of microglia sorted from tamoxifen treated adult Sall1CreER/fl mice and Sall1fl/fl control littermates. Microglia were obtained with > 98% purity and the absence of Sall1 was confirmed in Sall1CreER/fl microglia. We could show that deletion of Sall1 in microglia in vivo resulted in the conversion of these cells from resting tissue macrophages into inflammatory phagocytes leading to altered neurogenesis and disturbed tissue homeostasis. Similar changes in gene expression profiles were found in Sall1-deficient microglia isolated from tamoxifen-treated Cx3cr1CreERSall1fl/fl mice. In these mice, deletion of Sall1 is targeted to CX3CR1+ myeloid cells including microglia and CNS-associated macrophages but not to any other CNS-resident cells. This indicated that Sall1 transcriptional regulation maintains microglia identity and physiological properties in the CNS.

2016-10-19 | E-MTAB-5077 | biostudies-arrayexpress

Interleukin-1 signaling is involved in local self-renewal and maintenance of microglia

Project description:During early embryogenesis microglia arise from yolk sac progenitors populating the developing CNS, where they are maintained as tissue-resident macrophages throughout the organism’s lifespan. Here, we describe an experimental system that allows the specific conditional ablation of microglia in vivo. Strikingly, we found that the microglia compartment was reconstituted within one week following depletion. Microglia repopulation relied entirely on a CNS-resident, internal pool and was independent from bone marrow-derived precursors. Newly formed microglia were found in highly proliferative, organized micro-clusters that dissolve once steady state was achieved. Gene expression profiling revealed prominent expression of Interleukin-1 (IL-1) receptor in proliferating microglia. During the repopulation phase, IL-1 signaling was neutralized by treatment with IL-1 receptor antagonist that impaired microglia proliferation. Hence, microglia harbor a highly efficient potential to restore themselves without contribution of peripheral myeloid cells. IL-1 signaling significantly participates in this restorative proliferation process and is involved in stabilizing microglia maintenance. bone marrow macrophages, wild type microglia, and repopulating microglia

2015-07-15 | E-GEOD-68376 | biostudies-arrayexpress

Host microbiota constantly control maturation and function of microglia in the central nervous system (part 1)

Project description:As tissue macrophages of the central nervous system (CNS), microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. Here we reveal significant contributions of the host microbiota to microglia homeostasis as germ-free (GF) mice displayed global defects in microglia with altered cell proportions and an immature phenotype leading to impaired innate immune responses. Temporal eradication of host microbiota severely changed microglia properties. Limited microbiota complexity also resulted in defective microglia. In contrast, recolonization with a complex microbiota partially restored microglia features. We determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulate microglia homeostasis. Accordingly, mice deficient for the SCFA receptor FFAR2 mirrored microglia defects found under GF conditions. These findings reveal that host bacteria vitally regulate microglia maturation and function, whereas microglia impairment can be restored to some extent by complex microbiota. For acute inflammatory challenges, LPS was applied intracranially and 6 hours later, animals were analyzed. Control animals were injected PBS i.c. Transcriptional profiles of FACS-sorted microglia were assessed using Affymetrix® (Santa Clara, USA) GeneChip Arrays (Mouse Gene 2.1 ST Arrays).

2015-05-25 | E-GEOD-62201 | biostudies-arrayexpress

Testing data

Project description:Microglia are important immune cells in the central nervous system (CNS). Dysfunctions of gene-deficient microglia contribute to the development and progression of multiple CNS diseases. Microglia replacement by nonself cells has been proposed to treat microglia associated disorders. However, most of attempts are failed due to low replacement efficiencies, such as with the traditional bone marrow transplantation approach. In this study, we develop three efficient strategies for microglia replacement: microglia replacement by bone marrow transplantation (mrBMT), microglia replacement by peripheral blood (mrPB) and microglia replacement by microglia transplantation (mrMT). mrBMT and mrPB allow microglia-like cells to efficiently replace resident microglia in the whole CNS. On the other hand, mrMT achieves microglia replacement in brain regions of interest. In summary, the present study offers effective tactics for microglia replacement with diverse application scenarios, which potentially opens up a window on treating microglia-associated CNS disorders.

2023-07-31 | GSE136364 | GEO

Efficient strategies for microglia replacement in the central nervous system

2020-07-31 | GSE155499 | GEO

Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution

Project description:Microglia play critical roles in neural development and homeostasis. They are also implicated in neurodegenerative and neuroinflammatory diseases of the central nervous system (CNS). However, little is known about the presence of spatially and temporally restricted subclasses of microglia during CNS development and disease. Here, we combined massively parallel single-cell analysis, single-molecule FISH, advanced immunohistochemistry and computational modelling to comprehensively characterize novel microglia subclasses, which were transcriptionally different from perivascular macrophages, in up to six different CNS regions during development and diseases. Single-cell analysis revealed specific time- and region-dependent microglia subtypes during homeostasis. In contrast, demyelinating and neurodegenerative diseases evoked context-dependent microglia subtypes with distinct molecular hallmarks and diverse cellular kinetics. Finally, diverse microglia subsets were also identified in normal and diseased human brains. Our data provide new insights into the CNS endogenous immune system during development, health and perturbations.

2019-02-13 | GSE124335 | GEO

Gene expression analysis at single cell level from the CNS of mice that recieved B-NHL and treated with either Non Transduced (NT) or CD19 Chimeric Antigen Receptor (CAR) T cells

Project description:Microglia constitute the myeloid compartment of the Central Nervous System (CNS). scRNA sequencing was employed to decipher diverse microglia populations and other cell types from the cortex.

2024-02-20 | GSE223647 | GEO

Identification of a Unique TGF-β Dependent Molecular and Functional Signature in Microglia

Project description:Microglia are myeloid cells of the central nervous system (CNS) that participate both in normal CNS function and disease. We investigated the molecular signature of microglia and identified 239 genes and 8 microRNAs that were uniquely or highly expressed in microglia vs. myeloid and other immune cells. Out of 239 genes, 106 were enriched in microglia as compared to astrocytes, oligodendrocytes and neurons. This microglia signature was not observed in microglial lines or in monocytes recruited to the CNS and was also observed in human microglia. Based on this signature, we found a crucial role for TGF-β in microglial biology that included: 1) the requirement of TGF-β for the in vitro development of microglia that express the microglial molecular signature characteristic of adult microglia; and 2) the absence of microglia in CNS TGF-β1 deficient mice. Our results identify a unique microglial signature that is dependent on TGF-β signaling which provides insights into microglial biology and the possibility of targeting microglia for the treatment of CNS disease.

2013-07-08 | GSE48579 | GEO

Deterministic programming of human pluripotent stem cells into microglia facilitates studying their role in health and disease

Project description:Microglia, the resident immune cells of the central nervous system (CNS), are derived from yolk-sac macrophages that populate the developing CNS during early embryonic development. Once established, the microglia population is self-maintained throughout life by local proliferation. As a scalable source of microglia-like cells (MGLs), we here present a forward programming protocol for their generation from human pluripotent stem cells (hPSCs). The transient overexpression of PU.1 and C/EBPβ in hPSCs led to a homogenous population of mature microglia within 16 d. MGLs met microglia characteristics on a morphological, transcriptional, and functional level. MGLs facilitated the investigation of a human tauopathy model in cortical neuron–microglia cocultures, revealing a secondary dystrophic microglia phenotype. Single-cell RNA sequencing of microglia integrated into hPSC-derived cortical brain organoids demonstrated a shift of microglia signatures toward a more-developmental in vivo–like phenotype, inducing intercellular interactions promoting neurogenesis and arborization. Taken together, our microglia forward programming platform represents a tool for both reductionist studies in monocultures and complex coculture systems, including 3D brain organoids for the study of cellular interactions in healthy or diseased environments.

2022-09-16 | GSE207608 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data