Circadian transcriptome analysis in mouse cultured cortical astrocytes
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE254678 | GEO | 2024/11/26
REPOSITORIES: GEO
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Project description:Circadian transcriptome analysis in mouse cultured cortical astrocytes
| PRJNA1071502 | ENA
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:Cortical human fetal astrocytes, density 8-15000 cells/cm2 ( ScienCell, San Diego, CA, USA) seeded in Astrocyte medium (ScienCell, San Diego, CA, USA). Further info in "Proteomic and metabolomic characterization of human neurovascular unit cells in response to methamphetamine" Herland et al Adv Biosystems 2020
2020-07-23 | MSV000085817 | GNPS
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:An emerging link between circadian clock function and neurodegeneration has indicated a critical role for the molecular clock in brain health. We previously reported that deletion of the core circadian clock gene Bmal1 abrogates clock function and induces cell-autonomous astrocyte activation. Regulation of astrocyte activation has important implications for protein aggregation, inflammation, and neuronal survival in neurodegenerative conditions such as Alzheimer's disease (AD). Here, we investigated how astrocyte activation induced by Bmal1 deletion regulates astrocyte gene expression, amyloid-beta (Aβ) plaque-associated activation, and plaque deposition. To address these questions, we crossed astrocyte-specific Bmal1 knockout mice (Aldh1l1-CreERT2;Bmal1(fl/fl), termed BMAL1 aKO), to the APP/PS1-21 and the APP(NL-G-F) models of Aβ accumulation. Transcriptomic profiling showed that BMAL1 aKO induced a unique transcriptional profile affecting genes involved in both the generation and elimination of Aβ. BMAL1 aKO mice showed exacerbated astrocyte activation around Aβ plaques and altered gene expression. However, this astrogliosis did not affect plaque accumulation or neuronal dystrophy in either model. Our results demonstrate that the striking astrocyte activation induced by Bmal1 knockout does not influence Aβ deposition, which indicates that the effect of astrocyte activation on plaque pathology in general is highly dependent on the molecular mechanism of activation.
2023-03-14 | GSE227063 | GEO
Project description:General anesthesia is a common clinical procedure yet can result in long term CNS-adverse effects, particularly in the elderly, or dementia patients. Suppression of cortical activity is a key feature of the anesthetic-induced unconscious state, with activity being a well-described regulator of pathways important for brain health. However the extent to which the effects of anesthesia go beyond simple suppression of neuronal activity is incompletely understood, as are its effects on non-neuronal cell types such as astrocytes, which are important integrators of both neuronal activity and inflammatory signalling. In order to address these questions, we performed a combination of RNA-seq and TRAP-seq (Translating Ribosome Affinity Purification, where astrocyte-specific translating mRNAs are sequenced) on mouse cortical tissue and primary cortical neurons.
2023-08-01 | E-MTAB-13054 | biostudies-arrayexpress
Project description:Purpose: The core clock protein BMAL1 serves as the primary positive circadian transcriptional regulator and its depletion in astrocytes not only disrupts circadian function, but also leads to a unique cell-autonomous activation phenotype. We have undertaken RNAsequencing of isolated astrocytes from young wildtype and BMAL1 astrocyte-specific knockout mice (Bmal1fl/fl, ALDH1L1-CreERT2, termed BMAL1 aKO) to uncover changes to gene expression as a result of BMAL1 disruption in astrocytes. Methods: BMAL1 aKO mice and wildtype littermates were given tamoxifen at 2 months of age and harvested around 7 months of age and brains were collected. After collagenase digestion and debris removal, astrocytes were isolated from the rest of the brain cells (termed "flowthrough") using Miltenyi MACS Anti-ACSA-2 magnetic beads. RNA was extracted in Trizol reagent and sent for sequencing. Samples from BMAL1 aKO and wildtype astrocytes were compared and flowthrough samples were compared to astrocytes to confirm cell-type purity. Results: BMAL1 aKO results in both up- and down-regulation of many astrocyte genes. GO pathway analysis points to lysosomal pathways as dysregulated by knockout of BMAL1 in astrocytes. While astrocytes are enriched by our isolation methods, there is some degree of contamination from neurons and oligodendrocytes. Conclusions: While our astrocyte isolation method has some caveats in terms of purity, BMAL1 aKO appears to dysregulate lysosomal pathways, which will be investigated by further experiments.
2023-04-26 | GSE227633 | GEO
Project description:Purpose: The core clock protein BMAL1 serves as the primary positive circadian transcriptional regulator and its depletion in astrocytes not only disrupts circadian function, but also leads to a unique cell-autonomous activation phenotype. We have undertaken RNAsequencing of isolated astrocytes from aged wildtype and BMAL1 astrocyte-specific knockout mice (Bmal1fl/fl, ALDH1L1-CreERT2, termed BMAL1 aKO) to uncover changes to gene expression as a result of BMAL1 disruption in astrocytes and to confirm those changes persist during aging. Methods: BMAL1 aKO mice and wildtype littermates were given tamoxifen at 2 months of age and harvested around 20 months of age and brains were collected. After collagenase digestion and debris removal, astrocytes were isolated from the rest of the brain cells (termed "flowthrough") using Miltenyi MACS Anti-ACSA-2 magnetic beads. RNA was extracted in Trizol reagent and sent for sequencing. Samples from BMAL1 aKO and wildtype astrocytes were compared and flowthrough samples were compared to astrocytes to confirm cell-type purity. Results: BMAL1 aKO results in both up- and down-regulation of many astrocyte genes. GO pathway analysis points to lysosomal pathways as dysregulated by knockout of BMAL1 in astrocytes. While astrocytes are enriched by our isolation methods, there is some degree of contamination from neurons and oligodendrocytes. Conclusions: While our astrocyte isolation method has some caveats in terms of purity, BMAL1 aKO appears to dysregulate lysosomal pathways, which will be investigated by further experiments.
2023-04-26 | GSE227932 | GEO
Project description:Astrocytes are implicated in neuronal development, particularly excitatory synaptogenesis, but their genome-wide impact is unclear. Using cell-type specific RNA-seq we show that cortical astrocytes induce widespread transcriptomic changes in developing cortical neurons. Rat cortical neurons were maintained in the presence or absence of mouse astrocytes, RNA-seq performed, and mixed-species RNA-seq reads sorted according to species. Cultures were also treated with TTX to abolish neuronal firing activity, to investigate the effects of the presence or absence activity-dependent signalling.
2024-05-14 | E-MTAB-14070 | biostudies-arrayexpress
Project description:Astrocytes, the most abundant glial cell type in the brain, are underrepresented in traditional cortical organoid models due to the delayed onset of cortical gliogenesis. Here, we introduce a novel glia-enriched cortical organoid model that exhibits accelerated astrogliogenesis. We demonstrated that induction of a gliogenic switch in a subset of progenitors enabled rapid derivation of astroglial cells, which account for 25-31% of the cell population within eight to ten weeks of differentiation. Intracerebral transplantation of these organoids reliably generated a diverse repertoire of cortical neurons and anatomical subclasses of human astrocytes. Spatial transcriptome profiling identified layer-specific expression patterns among distinct subclasses of astrocytes within the organoid transplants. Using an in vivo acute neuroinflammation model, we identified a subpopulation of astrocytes that rapidly activates proinflammatory pathways upon cytokine stimulation. Additionally, we demonstrated that CD38 signaling plays a crucial role in mediating metabolic and mitochondrial stress in reactive astrocytes. This model provides a robust platform for investigating human astrocyte function.
2024-01-16 | GSE185472 | GEO