Single-cell transcriptome profiles of wild-type and IRF8KO microglia [scRNA-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE231405 | GEO | 2023/06/01
REPOSITORIES: GEO
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Project description:The role of the lineage-determining transcription factor IRF8 in microglia remains unelucidated. We report the genome-wide, transcriptome profiles of wild-type, IRF8KO, IRF8cKO, Batf3KO, 5xFAD, and 5xFAD/IRF8KO microglia. Deep-sequencing and subsequent differential analysis revealed the impacts of IRF8 on microglia-specific transcription programs, such as cell identity. Sall1 and Batf3 genes were identified as a downstream transcription factor of IRF8, and Batf3 dependent genes showed correlation with IRF8-dependent genes in microglia. The conditional depletion of IRF8 gene after microglial maturation (P14) increased or decreased the gene expression, most of which were shared with those of IRF8KO. This study provides a novel insight into understanding transcriptional programs in microglia.
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Project description:The role of the lineage-determining transcription factor, Interferon regulatory factor (IRF8), in microglia remains unelucidated. We report the genome-wide chromatin status in adult wild-type (WT) and IRF8-knockout (IRF8KO) microglia by ATAC-Seq. Deep-sequencing and subsequent differential analysis revealed that chromatin accessibility in microglia requires IRF8. At the same time, the loss of IRF8 gains aberrant chromatin accessibility that potentially confers mRNA transcription of the genes upregulated in IRF8KO microglia. This study provides a novel insight into understanding epigenetic regulation in microglia.
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Project description:The lineage-determining transcription factor IRF8's function in microglia is unclear. Our study aims to shed light on this by analyzing the genome-wide, temporal transcriptome profiles of wild-type and IRF8KO microglia. We used deep-sequencing and differential analysis to identify the effects of IRF8 on transcription programs in microglia, such as microglia identity gene expression. This study provides a new understanding of the transcriptional programs in microglia.
2024-07-01 | GSE266422 | GEO
Project description:The role of the lineage-determining transcription factor, Interferon regulatory factor (IRF8), in microglia remains elucidated. We report the genome-wide methyl-CpG status in adult wild-type (WT) and IRF8-knockout (IRF8KO) microglia by whole-genome bisulfite-Seq (WGBS). Deep-sequencing and subsequent differential analysis revealed that IRF8KO microglia exhibited a cell-intrinsic methylation profile. Furthermore, the differentially methylated regions showed a significant correlation with IRF8-dependent chromatin accessibility in microglia. This study provides a novel insight into understanding epigenetic regulation in microglia.
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Project description:The role of a transcription factor, Interferon Regulatory Factor 8 (IRF8), in microglia is yet to be fully understood. We conducted a study to examine the chromatin status of postnatal and adult wild-type (WT) and IRF8-knockout (IRF8KO) microglia through ATAC-Seq. We also added 5xFAD Alzheimer's disease microglia to observe any chromatin events that may be similar in disease-associated microglia. After deep-sequencing and differential analysis, we discovered that chromatin accessibility in microglia is dependent on IRF8. In the absence of IRF8, there was aberrant chromatin accessibility that potentially resulted in mRNA transcription of genes that were upregulated in IRF8KO microglia, which was distinct from 5xFAD microglia. This study contributes to a better understanding of epigenetic regulation in microglia.
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Project description:IRF8 is a transcription factor that is crucial in determining the lineage of microglia. We previously showed that IRF8 is robustly bound during the early postnatal period. To better understand IRF8's postnatal functions, we analyzed mice in which IRF8 was removed after P16. By using single-cell nuclei sequencing, we analyzed cells in which IRF8 was definitely knocked out and investigated both the transcriptome and chromatin accessibility that IRF8 regulates. The differential analysis showed the importance of IRF8 in regulating postnatal transcriptional programs and epigenetic landscapes that are related to microglial identity and disease-associated genes. This study provides a new perspective on how IRF8-mediated transcriptional programs affect microglia.
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Project description:The role of the lineage-determining transcription factor Interferon regulatory factor 8 (IRF8) in microglia remains elucidated. Here we report the genome-wide IRF8 binding profiles in microglia at various ages. CUT&RUN methodology revealed that IRF8 starts to bind to the genome around postnatal day 9 (P9), and its number increases with age. In comparison to peritoneal macrophages, microglia IRF8 showed a cell-intrinsic binding pattern. By co-occurrence analysis, most IRF8 was H3K4me1/H3K27ac-marked enhancers, and many of them bind to the H3K27ac(high) super-enhancer regions. In IRF8KO microglia, H3K4me1 and H3K27ac profiles were altered and deposited aberrantly on the genome. This study provides a novel insight into understanding epigenetic regulation in microglia.
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Project description:Preparation of primary microglial cultures from postnatal mice is tedious with a low yield, high variability and risk of astrocytic contamination. Microglia derived from embryonic stem cells (ESdM) have been suggested as alternative source, but it is unclear how closely ESdM resemble the molecular phenotype of primary microglia. Here, we performed a whole transcriptome analysis of ESdM in comparison to primary cultured and flow cytometry-sorted microglia and compared the microglial transcriptome to other cell types. Cultured microglia and ESdM were related to sorted microglia, but clearly distinct from other myeloid cell types, T cells, astrocytes and neurons. ESdM and primary cultured microglia showed strong overlap in their transcriptome. Only 144 gene transcripts were differentially expressed between both cell types, mainly derived from immune-related genes with a higher activation status of pro-inflammatory and immune defense genes in primary microglia compared to ESdM. Flow cytometry analysis of cell surface markers CD54, CD74 and CD274 selected from the microarray confirmed the close phenotypic relation between ESdM and primary cultured microglia. Thus, assessment of genome-wide transcriptional regulation demonstrates that microglia are distinct from other macrophage cell types and that mouse pluripotent stem cell-derived microglia are closely related to cultured postnatal microglia. Comparison of different primary neuronal cells with ES-cell derived microglial cells
2013-07-11 | E-GEOD-43808 | biostudies-arrayexpress
Project description:Microglia colonize the brain parenchyma at early stages of development and accumulate in specific regions where they actively participate in cell death, angiogenesis, neurogenesis and synapse elimination. A recurring feature of embryonic microglial distribution is their association with developing axon tracts which, together with in vitro data, supports the idea of a physiological role for microglia in neurite development. Yet the demonstration of this role of microglia is still lacking. Here, we have studied the consequences of microglial dysfunction on the formation of the corpus callosum, the largest connective structure in the mammalian brain, which shows consistent microglial accumulation during development. We studied two models of microglial dysfunction: the loss-of-function of DAP12, a key microglial-specific signaling molecule, and a model of maternal inflammation by peritoneal injection of LPS at E15.5. We performed transcriptional profiling of maternally inflamed and Dap12-mutant microglia at E17.5. We found that both treatments principally down-regulated genes involved in nervous system development and function, particularly in neurite formation. We then analyzed the functional consequences of these microglial dysfunctions on the formation of the corpus callosum. We also took advantage of the Pu.1-/- mouse line, which is devoid of microglia. We now show that all three models of altered microglial activity resulted in the same defasciculation phenotype. Our study demonstrates that microglia are actively involved in the fasciculation of corpus callosum axons. To investigate possible roles for microglial during brain development, we challenged microglial function by two complementary approaches. First, we induced maternal inflammation by peritoneal injection of LPS into pregnant dams. Next, we analyzed the consequences of a loss of function of DAP12, a signaling molecule specifically expressed in microglia that is crucial for several aspects of microglia biology (references in Wakselman et al., 2008). We compared the gene expression profiles of microglia from control, maternally-inflamed by LPS (MI), and Dap12-mutated embryos. We isolated RNA from FACS sorted maternally inflamed (by LPS) and Dap12-mutant microglia at E17.5 pooled per pregnant dam; as a control we included PBS treated and untreated (UT) microglia. We compared gene expression between maternally inflamed microlgia (PBSvsLPS) and DAP12-mutant microglia (UTvsDAP12KO).
2014-07-01 | E-GEOD-49079 | biostudies-arrayexpress
Project description:Japanese encephalitis virus (JEV) is a causative agent of encephalitis, mostly prevalent in Asia and South-Asian countries. Neuroinflammation is the hallmark of encephalitis, mediated in parts through the activation of brain-resident microglial cell, thus playing a critical role in determining pathogenesis. Deregulated activity of microglia can be lethal for the brain tissue. Interferon Regulatory Factor 8 (Irf8) mediates differentiation and transformation of microglia to reactive phenotypes and also regulates antiviral response through cross-talk with interferon pathway. In this study, we have conducted a comparative study between JEV infected C57BL/6 wild type and Irf8 Knockout (IRF8-/-) to identify the genes directly or indirectly regulated by IRF8.
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