Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Infiltrating monocyte-derived macrophages polarizes in to anti-inflammatory and neuro-protective phenotype in a rat model of cerebral ischemia

ABSTRACT: To summarize our results, we found microglia and MDMs are functionally heterogeneous population contributing differently to the disease phenotype. Our data, suggest that during post-ischemic inflammation microglia exhibit pro-inflammatory phenotype, while infiltrating MDMs display anti-inflammatory and neuro-protective phenotype. Apart from up-regulation of some of the classical M2 marker in MDMs, our gene expression profiling using RNA-sequencing revealed a unique signature of MDMs with the up-regulation of genes associated with wound healing, MHCII antigen-presentation and tissue repair. Our results strongly suggest that MDMs infiltrating the CNS parenchyma during the sub-acute of post-ischemic inflammation might contribute to the endogenous mechanism of neuroprotection.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE86941 | GEO | 2018/12/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Effect of peripherally-derived macrophages in adult microglia (mouse cells)

Project description:Infiltrating monocyte derived macrophages (MDMs) and resident microglia dominate CNS injury sites. We show that MDMs and microglia can directly communicate to modulate each other’s function. Also, the presence of MDMs in CNS injury suppresses microglia-mediated phagocytosis and inflammation. We suggest that macrophages infiltrating the injured CNS provide a mechanism to control acute and chronic microglia-mediated inflammation, which could otherwise drive damage in a variety of CNS conditions. To understand the global effects of macrophage communication to microglia, we transcriptionally profiled activated adult mouse microglia in the presence or absence of macrophages with and without an inflammatory stiumulus (LPS)

2018-08-01 | GSE102482 | GEO

Microglia coordinate cellular interactions during spinal cord repair

Project description:Traumatic spinal cord injury (SCI) triggers a neuro-inflammatory response dominated by tissue-resident microglia and monocyte derived macrophages (MDMs). Since activated microglia and MDMs are morphologically identical and express similar phenotypic markers in vivo, identifying injury responses specifically coordinated by microglia has historically been challenging. Here, we pharmacologically depleted microglia and use anatomical, histopathological, tract tracing, bulk and single cell RNA sequencing to reveal the cellular and molecular responses to SCI controlled by microglia. We show that microglia are vital for SCI recovery and coordinate injury responses in CNS-resident glia and infiltrating leukocytes. Depleting microglia exacerbates tissue damage and worsens functional recovery. Conversely, restoring select microglia-dependent signaling axes, identified through sequencing data, in microglia depleted mice prevents secondary damage and promotes recovery. Additional bioinformatics analyses reveal that optimal repair after SCI and likely other forms of neurological disease, might be achieved by co-opting key ligand-receptor interactions between microglia, astrocytes and MDMs.

2022-06-01 | GSE196928 | GEO

Resident microglia and infiltrating macrophages inflammatory, metabolic and sex-dependent gene-regulatory dynamics in the neonatal hippocampus after hypoxia-ischemia.

Project description:Neonatal hypoxia-ischemia (HI) is a major cause of perinatal death and long-term disabilities worldwide. Post-ischemic neuroinflammation, characterized by resident and infiltrating immune cells, plays a pivotal role in HI pathophysiology. However, the specific modulatory roles of resident microglia and blood-derived macrophages remain poorly understood. In the present study, we investigated the temporal dynamics of microglia (CX3CR1GFP/+) and infiltrating macrophages (CCR2RFP/+) in the hippocampi of mice subjected to HI at postnatal day (PND) 9. We reveal an increase of CX3CR1GFP+ resident cells in the injured hippocampi soon after HI, peaking at three days post injury. In contrast, infiltration of CCR2RFP/+ cells peaked one day after HI and gradually decreased over time. Transcriptomic signatures of CX3CR1GFP/+ and CCR2RFP/+ cells isolated from hippocampi showed a partial convergence at day 3, through cell type - specific dynamics. Using inflammatory pathway and transcription factor analyses, we identify a distinct post-ischemic response in CCR2RFP/+ cells characterized by differential gene expression in sensome, homeostatic, matrisome, lipid metabolic and inflammatory molecular signatures as consequence of HI. Finally, we identified a sexual dimorphism in CX3CR1GFP/+ cells, where microglia unique genes in males but not in females returned to homeostatic levels comparable to controls three days after HI. In conclusion, our results indicate that CX3CR1GFP/+ and CCR2RFP/+ cells have diverse roles in orchestrating the inflammatory cascade after HI, and that infiltrating macrophages drive post-ischemic inflammation.

2023-07-26 | GSE238220 | GEO

Longitudinal scRNA-Seq of immune cells from GL261 murine brain Tumors and MHC class II deficient tumor-mircoenvironments

Project description:Longitudinal phenotyping of T cells and myeloid cells in early (day 14) and late (day26) GL261 tumors. Single cell RNA sequencing of CD45+ immune cell from intracranial murine GL261-SIINFEKL tumors 20 days after inoculation. SIINFEKL-reactive T cells were sorted based on dextramer staining. Using time-resolved scRNA-seq of murine tumor-infiltrating immune cells from early (d14) and late stage (d26) syngeneic GL261 gliomas we observed constant MHCII expression by murine microglia over time and overall high but decreasing MHCII expression in late stage bbm indicating a dynamic process of MHCII expression. We show that loss of major histocompatibility complex (MHC) class II (MHCII)-restricted antigen presentation on bbm drives dysfunctional intratumoral tumor-reactive CD8+ T cell states through increased expression of Tox, a critical regulator of T cell exhaustion. By calculating the normalized abundance of T cell states along the pseudotime trajectory of SIINFEKL-reactive CD8+ T cells retrieved from myeloidMHCII-proficient and -deficient microenvironments, we found an enrichment of a distinct T cell state in myeloidMHCIIKO CD8+ T cells that was defined by peak expression of exhaustion markers. Mechanistically, MHCII-dependent activation of CD4+ T cells restricts myeloid-derived osteopontin that triggers a chronic activation of nuclear factor of activated T cells (Nfat)2 in tumor-reactive CD8+ T cells. In summary, we provide evidence that MHCII-restricted antigen presentation on bbm is a key mechanism to directly maintain functional cytotoxic T cell states in brain tumors.

2023-01-19 | E-MTAB-12523 | biostudies-arrayexpress

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.

2020-11-04 | GSE136001 | GEO

RNA-Seq transcriptome comparison of microglia and CD11c+ cells sorted from the ischemic brain tissue of parabiotic (female) mice

Project description:RNA-Seq transcriptome comparison of the following cell populations (n=3-4 independent samples per cell population): a) CD11c-eYFP+ cells FACS sorted from brain of female adult mice 4 days after cerebral ischemia, b) CD11c-eYFP+ cells FACS sorted from brain of female parabiotic mice 4 days after cerebral ischemia c) CX3CR1+ microglia sorted from the ischemic brain of female CX3CR1CreERT2-ROSA26 tdTomato mice. Purpose: The goal of this study is to compare the transcriptome profile (RNA-Seq) of infiltrating cD11c-eYFP+ cells and microglia, both collected from ischemic brains of mice. Methods: RNA samples were obtained from FACS sorted eYFP+ cells of the ipsilateral brain hemisphere of CD11c-eYFP mice 4 days post-ischemia, the ipsilateral brain hemisphere of CD11c-eYFP/WT parabiotic mice 4 days post-ischemia, and from microglial cells sorted from the ipsilateral brain hemisphere of Cx3cr1CreERT2:ROSA26dTomato mice 4 days post-ischemia. NGS was performed (RNA-Seq) to compare the transcriptome of these populations. Results: the populations we compared clearly separated the differentially expressed genes in an unsupervised cluster analysis. 1509 genes were overrepresented in microglia and 1183 genes were overrepresented in CD11c-eYFP+ cells in the ischemic brain. Conclusions: Our study is the first comparative analysis of the transcriptomes of microglia and the infiltrating CD11c-eYFP+ cells derived from the ischemic brain of mice. The results show that the infiltrating CD11c-eYFP cell population in the ischemic brain tissue of parabiotic mice displays overrepresentation of genes typical of dendritic cells, immune functions, and ClassII antigen presentation, amongst others, that are not found represented in microglia.

2020-10-20 | GSE136855 | GEO

Microglia and infiltrating monocytes gene expression profiling during EAE progress

Project description:The project was designed to figure out the role of microglia in brain inflammation (EAE model). The first step was to find genes/pathways that are upregulated in the microglia during EAE progress but absent in the infiltrating monocytes. These genes/pathways may provide clues for studying the unique function of microglia in the brain inflammation that is disctinct from the infiltrating monocytes.

2019-12-05 | GSE133180 | GEO

LPS-induced systemic inflammation mediates a protective effect against ischemic injury via microglia

Project description:LPS-induced systemic inflammation mediates a protective action on ischemic injury via microglia. We used RNA sequencing analysis (RNA-seq) to gain molecular insights into microglia-mediated protection of cerebral infarction.

2023-12-19 | GSE244358 | GEO

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

Project description:Microglia are resident myeloid cells in the central nervous system (CNS) that regulate homeostasis and protect CNS from damage and infection. The phenotype of microglia is critical in regulating the propagation and resolution of inflammatory responses after ischemic stroke. However, little is known of its complexity and heterogeneity in the above context. Here, using single-cell RNA sequencing (scRNA-seq) of over 11,000 cells from the mice ischemic brain tissues, we demonstrated a previously undefined molecular heterogeneity among microglia clusters following ischemic stroke.

2023-06-14 | GSE210986 | GEO

MHC class II antigen presentation by tumoral lymphatics is required for tumor specific signature and suppressive functions of Tregs

Project description:A number of solid malignancies triggers lymphangiogenesis, facilitating metastasis. Recent studies further indicate that tumor-associated lymphatic vessels significantly contribute to the generation of an immunosuppressive tumor microenvironment. Here, we have investigated the ability of tumor-associated lymphatic endothelial cells (LECs) to function as MHC class II restricted antigen-presenting cells in the regulation of anti-tumor immunity. Using murine models of lymphangiogenic tumors engrafted under the skin, we show that tumor LECs upregulate MHCII and the MHCII antigen processing machinery, and promote Treg expansion ex vivo. Using mice with a LEC-restricted lack of MHCII expression, we demonstrate that tumor growth is severely impaired, whereas tumor-infiltrating T effector cells are increased. Reduction of tumor growth and reinvigoration of tumor-specific T cell responses both result from alterations of the tumor-infiltrating regulatory T cell (Treg) transcriptome and phenotype. Treg suppressive functions are consequently profoundly altered in tumors lacking MHCII in LECs. No difference in effector T cell responses or Treg phenotype and functions were observed in tumor-draining lymph nodes, indicating that MHCII restricted antigen presentation by LECs is required locally in the tumor microenvironment (TME) to confer potent suppressive functions to Tregs. Altogether, our study advocates a role for MHCII-restricted antigen-presenting tumor LECs that function as a local brake, dampening tumor T cell immunity and promoting intratumoral Treg suppressive functions.

2024-03-01 | GSE168609 | 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