Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Novel transcriptomic microglia taxonomy across mouse and human pathologies

ABSTRACT: Microglia are the key immune cells involved in virtually all diseases of the central nervous system (CNS). Numerous previous single-cell sequencing approaches to the study of microglia have revealed extensive diversity in this cell type in the human and mouse brain in different conditions. Importantly, a unifying, comprehensive, disease- and species spanning transcriptomic immune cell-focused atlas of the perturbed CNS, including true single-cell spatial transcriptomic information on neighborhood relationships, is lacking. Here, we generated a novel large-scale single-cell RNA-sequencing-derived taxonomy through the analysis of > 1 million CNS cells enriched for myeloid cells across > 30 different pathologies and conditions. Disease-associated human microglia, together with CNS-associated macrophages and monocytes, were differentiated iteratively into 27 superclusters and 192 clusters, showing substantial overlap with their counterparts in the corresponding murine pathologies. This top-down approach, in combination with targeted and genome-wide subcellular spatial transcriptomics, enabled us to examine and compare the spatial interactome of the identified superclusters and clusters within and across pathologies and species. Using cell-specific mutants, we further characterized the underlying transcriptional programs of activation-associated microglial clusters, identifying distinct dependencies on type I and II interferons and colony stimulating factor 1 receptor pathways. Our data provide new insights into the spatial dynamics of the endogenous CNS immune system during development, health and disease in human and mouse.

ORGANISM(S): Mus musculus

PROVIDER: GSE304010 | GEO | 2026/02/09

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

T cell - DAM feedback loop drives CNS inflammation and neurodegenration in SPG15 at an early age [CD45+]

Project description:The immune system is an emerging cause of neuroinflammation and is suspected to be involved in neurodegeneration. The role of microglia, the macrophages of the Central Nervous System (CNS), was extensively researched in CNS neuropathologies. However, we only start to understand the role of T cells in diseases like Alzheimer’s Disease (AD) and Huntington’s Disease (HD) and how microglial – T cell crosstalk contributes to these pathologies. Here we tackle these topics in a rare and less investigated disease called Spastic Paraplegia 15 (SPG15) using a Zfyve26-/- mouse model. We were able to show, that CD8+ T cells and microglia potentiate a pro-inflammatory response through bidirectional communication in SPG15 KO and not WT mouse brains. The increase of CD8+ T cells in SPG15 KO animals also required a TCR dependent component. These findings are in line with previous reports on neurodegenerative disease which hints at cross-condition mechanisms involved in CD8+T cell responses in CNS, when encountering accumulation of non-degradable material in the brain.

2025-04-04 | GSE244476 | GEO

T cell - DAM feedback loop drives CNS inflammation and neurodegenration in SPG15 at an early age via CCR5-CCL5 interaction [CD3+]

2025-04-04 | GSE244474 | GEO

Mapping microglia diversity in the human brain through the integration of high-dimensional techniques

Project description:Microglia are tissue-resident macrophages of the central nervous system (CNS) that orchestrate local immune responses and contribute to several neurological and psychiatric diseases. Little is known about human microglia and how they orchestrate their highly plastic, context-specific adaptive responses during pathology. Here, we combined two high-dimensional technologies, single-cell RNA-sequencing (scRNA-seq) and time-of-flight mass cytometry (CyTOF), to identify microglia states in the human brain during homeostasis and disease. This approach enabled us to identify and characterize a previously unappreciated spectrum of transcriptional states in human microglia. These transcriptional states are determined by their spatial distribution, and they further change with aging and brain tumor pathology. The description of multiple microglia phenotypes in the human CNS may open promising new avenues for subset-specific therapeutic interventions.

2019-11-18 | GSE135437 | GEO

IL-10 prevents pathological microglia hyperactivation following peripheral endotoxin challenge

Project description:Microglia, the resident macrophages of the brain parenchyma, are central players in CNS development, homeostasis and disorders. Distinct brain pathologies seem associated with discrete microglia activation modules. How microglia regain their ground state following challenges remains much less understood. Here, we explored the role of the IL-10 axis in restoring murine microglia homeostasis following peripheral endotoxin challenge. Specifically, we show that lipopolysaccharide (LPS)-challenged mice harboring IL-10 receptor-deficient microglia display neuronal impairment and succumb to fatal sickness. Addition of a microglial TNF deficiency rescues these animals, suggesting a microglia-based circuit driving pathology. Single cell transcriptome analysis revealed various IL-10 producing resident and recruited immune cell in the CNS, including most prominently Ly49D+ NK cells and neutrophils, but not microglia. Collectively, we define the kinetics of the microglia response to peripheral endotoxin challenge, including their activation and robust silencing, and highlight the critical role of non-microglial IL-10 in preventing deleterious microglia hyperactivation.

2020-10-22 | GSE157480 | GEO

Novel transcriptomic microglia taxonomy across mouse and human pathologies

Project description:Novel transcriptomic microglia taxonomy across mouse and human pathologies

| PRJNA1298755 | ENA

Microglia-derived TGF-β1 ligand maintains microglia homeostasis via autocrine mechanism and is critical for normal cognitive function in adult mouse brain

Project description:While TGF-β signaling is essential for microglial function, the cellular source of TGF-β ligand and its spatial regulation remains unclear in adult CNS. Our data supports that microglia but not astrocytes or neurons are the primary producers of TGF-β1 ligands needed for microglial homeostasis. Microglia-Tgfb1 KO leads to activation of microglia featuring a dyshomeostatic transcriptomic profile that resembles disease-associated microglia (DAMs), injury-associated microglia, and aged microglia, suggesting that microglial self-produced TGF-β1 ligands are important in the adult CNS. Interestingly, astrocytes in the MG-tgfb1 iKO mice show a transcriptome profile that is closely aligned with A1-like astrocytes. Additionally, using sparse mosaic single cell microglia KO of TGF-β1 ligand we established an autocrine mechanism for TGF-β signaling. Importantly MG-Tgfb1 inducible KO mice show cognitive deficits, supporting that precise spatial regulation of TGF-β1 ligand derived from microglia is critical for the maintenance of brain homeostasis and normal cognitive function in the adult brain.

2023-08-08 | GSE236032 | GEO

Microarray analysis to evaluate the function of USP18 in the mouse CNS

Project description:Microglia are tissue macrophages of the central nervous system (CNS) that control tissue homeostasis, and as such they are crucially important for organ integrity. Microglia dysregulation is thought to be causal for a group of neuropsychiatric, neurodegenerative and neuroinflammatory diseases, called ‚Äòmicrogliopathies‚Äô. However, how the intracellular stimulation machinery in microglia is controlled is poorly understood. By using expression studies, we identified the ubiquitin-specific protease (Usp) 18 in white matter microglia that essentially contributes to microglial quiescence under homeostatic conditions. We further found that microglial Usp18 negatively regulated the activation of STAT1 and concomitant induction of interferon-induced genes thereby disabling the termination of IFN signalling. Unexpectedly, the Usp18-mediated feedback loop was independent from the catalytic domain of the protease but instead required the interacting region of Ifnar2. Additionally, the absence of Ifnar1 completely rescued microglial activation indicating a tonic IFN signal mediated by receptor interactions under non-diseased conditions. Finally, conditional depletion of Usp18 only in myeloid cells significantly enhanced the disease burden in a mouse model of CNS autoimmunity, increased axonal and myelin damage and determined the spatial distributions of CNS lesions that shared the same STAT1 signature as myeloid cells found in active multiple sclerosis (MS) lesions. These results identify Usp18 as novel negative regulator of microglia activation, demonstrate a protective role of the IFNAR pathway for microglia and establish Usp18 as potential therapeutic target for the treatment of MS. Brain lysate of adult WT, USP18ko, IFNAR1ko and USP18ko:IFNARko mice were analyzed

2015-04-20 | E-GEOD-61499 | biostudies-arrayexpress

Microarray analysis to evaluate the role of USP18 in primary microglia and the microglia cell line BV-2

Project description:Microglia are tissue macrophages of the central nervous system (CNS) that control tissue homeostasis, and as such they are crucially important for organ integrity. Microglia dysregulation is thought to be causal for a group of neuropsychiatric, neurodegenerative and neuroinflammatory diseases, called ‘microgliopathies’. However, how the intracellular stimulation machinery in microglia is controlled is poorly understood. By using expression studies, we identified the ubiquitin-specific protease (Usp) 18 in white matter microglia that essentially contributes to microglial quiescence under homeostatic conditions. We further found that microglial Usp18 negatively regulated the activation of STAT1 and concomitant induction of interferon-induced genes thereby disabling the termination of IFN signalling. Unexpectedly, the Usp18-mediated feedback loop was independent from the catalytic domain of the protease but instead required the interacting region of Ifnar2. Additionally, the absence of Ifnar1 completely rescued microglial activation indicating a tonic IFN signal mediated by receptor interactions under non-diseased conditions. Finally, conditional depletion of Usp18 only in myeloid cells significantly enhanced the disease burden in a mouse model of CNS autoimmunity, increased axonal and myelin damage and determined the spatial distributions of CNS lesions that shared the same STAT1 signature as myeloid cells found in active multiple sclerosis (MS) lesions. These results identify Usp18 as novel negative regulator of microglia activation, demonstrate a protective role of the IFNAR pathway for microglia and establish Usp18 as potential therapeutic target for the treatment of MS. Primary microglia (WT, USP18ko and USP18_C61A mice) and BV-2 cells (treated with control siRNA or siRNA against USP18) were incubated with 500 U/ml IFN-b. At different timepoints (0h, 6h, and 24h) RNA samples were taken and analyzed via Microarray

2015-04-20 | E-GEOD-61500 | 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

Genoma-wide analysis of pro- and anti-inflammatory activation states in primary microglia.

Project description:Murine primary microglia were treated with different inflammatory stimulants to induce different activation states and analyze the associated transcriptional changes. Abstract: Microglia, the immune cells of the CNS, are highly adaptive cells that can acquire different pro- and anti-inflammatory activation states with distinct functions in CNS homeostasis and pathologies. To study microglial function in vitro, primary microglia or immortalized cell lines are commonly used. An alternative to these cells are embryonic stem cell-derived microglia (ESdM). ESdM have previously been shown to be very similar to primary microglia in terms of expression profiles and surface molecules. In this study, ESdM and primary microglia were treated with different inflammatory stimulants to analyze their ability to adopt different activation states. Using quantitative real time PCR, comparative transcriptomics, ELISA, and flow cytometry, we found that different activation states can be induced in ESdM, which are similar to those found in primary microglia. These states are characterized by specific sets of inflammatory marker molecules and differential transcriptome signatures. Our results show that ESdM are a valuable alternative cell model to study microglial functions and neuroinflammatory mechanisms.

2016-06-19 | GSE77064 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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