Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA300968 | ENA |
REPOSITORIES: ENA
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Project description:GFAP and vimentin deficiency alters gene expression in astrocytes and microglia in wild-type mice and changes the transcriptional response of reactive glia in mouse model for Alzheimer's disease. Reactive astrocytes with an increased expression of intermediate filament (IF) proteins Glial Fibrillary Acidic Protein (GFAP) and Vimentin (VIM) surround amyloid plaques in Alzheimer's disease (AD). The functional consequences of this upregulation are unclear. To identify molecular pathways coupled to IF regulation in reactive astrocytes, and to study the interaction with microglia, we examined WT and APPswe/PS1dE9 (AD) mice lacking either GFAP, or both VIM and GFAP, and determined the transcriptome of cortical astrocytes and microglia from 15- to 18-month-old mice. Genes involved in lysosomal degradation (including several cathepsins) and in inflammatory response (including Cxcl5, Tlr6, Tnf, Il1b) exhibited a higher AD-induced increase when GFAP, or VIM and GFAP, were absent. The expression of Aqp4 and Gja1 displayed the same pattern. The downregulation of neuronal support genes in astrocytes from AD mice was absent in GFAP/VIM null mice. In contrast, the absence of IFs did not affect the transcriptional alterations induced by AD in microglia, nor was the cortical plaque load altered. Visualizing astrocyte morphology in GFAP-eGFP mice showed no clear structural differences in GFAP/VIM null mice, but did show diminished interaction of astrocyte processes with plaques. Microglial proliferation increased similarly in all AD groups. In conclusion, absence of GFAP, or both GFAP and VIM, alters AD-induced changes in gene expression profile of astrocytes, showing a compensation of the decrease of neuronal support genes and a trend for a slightly higher inflammatory expression profile. However, this has no consequences for the development of plaque load, microglial proliferation, or microglial activation. 2 cell types from 6 conditions: cortical microglia and cortical astrocytes from 15-18 month old APPswe/PS1dE9 mice compared to wildtype littermates. Biological replicates: microglia from APPswe/PS1dE9, N=7, microglia from WT, N=7, astrocytes from APPswe/PS1dE9, N=4, microglia from WT, N=4
2015-11-04 | E-GEOD-74614 | biostudies-arrayexpress
Project description:Acutely isolated murine cortical astrocytes and microglia: Alzheimer's disease vs wildtype
| PRJNA300967 | ENA
Project description:GFAP and vimentin deficiency alters gene expression in astrocytes and microglia in wild-type mice and changes the transcriptional response of reactive glia in mouse model for Alzheimer's disease. Reactive astrocytes with an increased expression of intermediate filament (IF) proteins Glial Fibrillary Acidic Protein (GFAP) and Vimentin (VIM) surround amyloid plaques in Alzheimer's disease (AD). The functional consequences of this upregulation are unclear. To identify molecular pathways coupled to IF regulation in reactive astrocytes, and to study the interaction with microglia, we examined WT and APPswe/PS1dE9 (AD) mice lacking either GFAP, or both VIM and GFAP, and determined the transcriptome of cortical astrocytes and microglia from 15- to 18-month-old mice. Genes involved in lysosomal degradation (including several cathepsins) and in inflammatory response (including Cxcl5, Tlr6, Tnf, Il1b) exhibited a higher AD-induced increase when GFAP, or VIM and GFAP, were absent. The expression of Aqp4 and Gja1 displayed the same pattern. The downregulation of neuronal support genes in astrocytes from AD mice was absent in GFAP/VIM null mice. In contrast, the absence of IFs did not affect the transcriptional alterations induced by AD in microglia, nor was the cortical plaque load altered. Visualizing astrocyte morphology in GFAP-eGFP mice showed no clear structural differences in GFAP/VIM null mice, but did show diminished interaction of astrocyte processes with plaques. Microglial proliferation increased similarly in all AD groups. In conclusion, absence of GFAP, or both GFAP and VIM, alters AD-induced changes in gene expression profile of astrocytes, showing a compensation of the decrease of neuronal support genes and a trend for a slightly higher inflammatory expression profile. However, this has no consequences for the development of plaque load, microglial proliferation, or microglial activation.
2015-11-04 | GSE74614 | GEO
Project description:Isolation of glia from Alzheimer's mice reveals inflammation and dysfunction. Reactive astrocytes and microglia are associated with amyloid plaques in Alzheimer's disease (AD). Yet, not much is known about the molecular alterations underlying this reactive phenotype. To get an insight into the molecular changes underlying AD induced astrocyte and microglia reactivity, we performed a transcriptional analysis on acutely isolated astrocytes and microglia from the cortex of aged controls and APPswe/PS1dE9 AD mice. As expected, both cell types acquired a proinflammatory phenotype, which confirms the validity of our approach. Interestingly, we observed that the immune alteration in astrocytes was relatively more pronounced than in microglia. Concurrently, our data reveal that astrocytes display a reduced expression of neuronal support genes and genes involved in neuronal communication. The microglia showed a reduced expression of phagocytosis and/or endocytosis genes. Co-expression analysis of a human AD expression data set and the astrocyte and microglia data sets revealed that the inflammatory changes in astrocytes were remarkably comparable in mouse and human AD, whereas the microglia changes showed less similarity. Based on these findings we argue that chronically proinflammatory astrocyte and microglia phenotypes, showing a reduction of genes involved in neuronal support and neuronal signaling, are likely to contribute to the neuronal dysfunction and cognitive decline in AD. 2 cell types from 2 conditions: cortical microglia and cortical astrocytes from 15-18 month old APPswe/PS1dE9 mice compared to wildtype littermates. Biological replicates: microglia from APPswe/PS1dE9, N=7, microglia from WT, N=7, astrocytes from APPswe/PS1dE9, N=4, microglia from WT, N=4
2015-11-04 | E-GEOD-74615 | biostudies-arrayexpress
Project description:We have generated a tuberous sclerosis complex (TSC) mouse model through mouse Gfap-Cre mediated conditional knockout of Tsc1 gene. Tsc1 depletion occurs in most astrocytes and a fraction of upper cortical and hippocampal neurons. The mice develop spontaneous seizures after 10 weeks of age. To determine the effect of Tsc1 deficiency on astrocytes, we compared astrocyte gene expressio profiles between mGfap-Cre:Tsc1CKO and littermate control mice at 4 weeks and 15 weeks of age. At 4 weeks, mGfap-Cre:Tsc1CKO mice showed increased transcription of a few astrocyte genes, including Vim, Amigo2, Thbs4, Slc7a11, Gjb6 and ALDH1L1, and there were not changes in protein products of these genes. At 15 Weeks, mGfap-Cre:Tsc1CKO mice with seizures showed increased transcription of reactive astrocyte genes, including Gfap, Vim, CD44, Sparc, Serpina3n and many others. The transcriptional changes were consistent with enhanced protein levels.
2021-08-31 | GSE156891 | GEO
Project description:Isolation of glia from Alzheimer's mice reveals inflammation and dysfunction. Reactive astrocytes and microglia are associated with amyloid plaques in Alzheimer's disease (AD). Yet, not much is known about the molecular alterations underlying this reactive phenotype. To get an insight into the molecular changes underlying AD induced astrocyte and microglia reactivity, we performed a transcriptional analysis on acutely isolated astrocytes and microglia from the cortex of aged controls and APPswe/PS1dE9 AD mice. As expected, both cell types acquired a proinflammatory phenotype, which confirms the validity of our approach. Interestingly, we observed that the immune alteration in astrocytes was relatively more pronounced than in microglia. Concurrently, our data reveal that astrocytes display a reduced expression of neuronal support genes and genes involved in neuronal communication. The microglia showed a reduced expression of phagocytosis and/or endocytosis genes. Co-expression analysis of a human AD expression data set and the astrocyte and microglia data sets revealed that the inflammatory changes in astrocytes were remarkably comparable in mouse and human AD, whereas the microglia changes showed less similarity. Based on these findings we argue that chronically proinflammatory astrocyte and microglia phenotypes, showing a reduction of genes involved in neuronal support and neuronal signaling, are likely to contribute to the neuronal dysfunction and cognitive decline in AD.
2015-11-04 | GSE74615 | GEO
Project description:To investigate astrocyte-microglia interactions in vivo, we took advantage of the recombinant rabies virus (RV). We used glycoprotein G-deficient RV expressing the fluorescent protein mCherry and pseudotyped with glycoprotein EnvA, in combination with GFAP-Cre RABVgp4/TVA transgenic mice that express TVA protein and glycoprotein G in astrocytes under the control of the Gfap promoter. Following injection into GfapRABVgp4/TVA mice, RV initially infects TVA expressing astrocytes, and following its replication RV infect cells in direct contact with astrocytes. We then sorted mCherry+ or mCherry- microglia on EAE mice and prove that microglia that had interacted with astrocytes had a more proinflammatory transcriptional profile.
2022-02-25 | GSE149107 | GEO
Project description:To examine the effect of Nf1 inactivation in astrocytes on normal microglia in the optic nerve, microglia from Nf1 flox/flox (FF) and Nf1 flox/flox; GFAP-Cre (FFC) were flow sorted. High throughput RNA-seq was employed to compare the expression profiles, and upregulated genes in microglia supportive to Nf1 deficient astrocytes were verified.
2020-07-03 | GSE65865 | GEO
Project description:Here, we use a series of genetically-defined murine cortical astrocytes with conditional inactivation of Rb/Pten and activated Kras to systematically investigate the individual and combinatorial roles of these pathways during gliomagenesis. We show that genetic disruption of all three pathways, which frequently occurs in human GBM, leads to maximal in vitro growth, migration, and invasion and produces stem-like transcriptomal profiles similar to the proneural subtype of human GBM. Genetic alterations in all three pathways are also required for efficient tumorigenesis in an orthotopic syngeneic allograft model system in vivo. These findings show that cortical astrocytes can form GBM and identify a potential model for proneural GBM that can be used to test subtype-specific therapies. Transcriptional profiling of transformed murine cortical astrocytes shows correlation between mutated genes, invasive capability, neural lineage, and human astrocytoma/GBM signatures. 10 samples Cortical astrocytes were isolated from neonatal mice (C57BL/6 background strain) and cultured. Cells were infected with adeneoviral-Cre for 6 hours to induce recombination. This resulted in expression of an N-terminal 121 amino acid truncation mutant of SV40 large T antigen (T121, hereafter called T) from the human glial fibrillary acidic protein (GFAP) promoter, which inactivates all three members of the Rb family (Rb, p107, p130) and results in proliferation and defective G1/S ratios. Additionally, cells contained KrasG12D mutant (R) and/or contained either heterozygous or homozygous deletion of Pten (P+/- or P-/-) . Here are 23 cell lines comprising 6 different genotypes. 10 Samples (Sample Title: TR_2, T_1, TRP_null_3, TR_1, TRP_null_4, TRP_het_1, T_2, TRP_null_2, T_3, TRP_null_5) from one batch were combined with the remaining 13 samples to remove batch related effects (see data processing for method).
2013-06-30 | E-GEOD-40265 | biostudies-arrayexpress
Project description:Expression profiles for Gfap-positive astrocytes obtained by in vitro differentiation of 129SvJae x C57BL/6 murine embryonic stem (ES) cells. Generated to examine the relationship between expression levels and DNA methylation patterns. Experiment Overall Design: 3 replicates of ES-derived astrocytes.
2008-10-20 | E-GEOD-11483 | biostudies-arrayexpress