Ethanol exposure reveals persistent and categorizable astrocyte calcium response types and associated gene signatures
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA818028 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18391000_1.fastq.gz | Fastqsanger.gz | |||
| SRR18391000_2.fastq.gz | Fastqsanger.gz | |||
| SRR18391001_1.fastq.gz | Fastqsanger.gz | |||
| SRR18391001_2.fastq.gz | Fastqsanger.gz | |||
| SRR18391002_1.fastq.gz | Fastqsanger.gz |
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Project description:Various EtOH doses increased intracellular calcium in a subset of astrocytes, identifying three cellular response types categorized by response waveform properties S- (sustained), T- (transient), or M- (Mixed), along with non-responsive (NR) astrocytes. By single-cell RNA-seq analysis of astrocytes from the different response types, we report type-enriched discriminatory gene expression signatures and provide a basis for identifying the relationship between susceptibility to EtOH effects in the astrocyte subgroups and corresponding measurable markers of calcium signal and gene expression.
2022-07-27 | GSE199025 | GEO
Project description:Inflammation features in diverse central nervous system disorders such as stroke, trauma, neurodegeneration, infection and autoimmunity. To better understand how inflammatory mediators may alter astrocyte functions, we examined the effects of transforming growth factor-β1 (TGF-β1), lipopolysaccharide (LPS) and interferon-gamma (IFNγ) on purified, murine, primary cortical astrocyte cultures. We used microarrays to conduct whole genome expression profiling, and measured calcium signaling, which is implicated in mediating dynamic astrocyte functions. Combinatorial exposure to TGF-β1, LPS and IFNγ significantly modulated astrocyte expression of over 6,800 genes and resulted in both additive and synergistic changes compared with individual stimuli alone. Bioinformatic analysis revealed that combinatorial treatment significantly and markedly up regulated molecular networks and pathways associated with immune signaling and with regulation of cell compromise, death, growth and proliferation. These findings provide databases of astrocyte transcriptome changes elicited by the inflammatory stimuli, TGF-β1, LPS and IFNγ alone and in combination, and show that these stimuli up regulate astrocyte molecular networks associated with immune- and injury-related functions and significantly alter astrocyte calcium signaling evoked by multiple GPCR. We used microarrays to examine the effects of transforming growth factor-β1 (TGF-β1), lipopolysaccharide (LPS) and interferon-gamma (IFNγ) on purified, murine, primary cortical astrocyte cultures.
2012-10-18 | E-GEOD-36089 | biostudies-arrayexpress
Project description:The role astrocytes play in brain development and function has come under increased focus as the diversity of roles they are involved in has become apparent. We have previously shown ethanol exposed astrocytes alter neuronal neurite outgrowth in an in vitro co-culture system and that ethanol alters the astrocyte produced extracellular matrix (ECM) in vitro, with similar alterations in vivo. Here we utilize the translating ribosome affinity purification (TRAP) procedure in Aldh1l1-EGFP/Rpl10a transgenic mouse primary cortical astrocyte cultures to transcriptionally and translationally profile the astrocyte response to ethanol. We found large differences in the total RNA pool in comparison to the translating RNA pool while the ethanol response within each pool showed a large degree of overlap. Comparisons to published datasets indicate the in vitro model used here are most similar to PD1-PD7 in vivo cortical astrocytes and the ethanol regulated genes showed significant overlap with models of chronic ethanol exposure in astrocytes and a model of third-trimester ethanol exposure in the hippocampus and cerebellum. These findings will further our understanding of the effects of ethanol on astrocyte gene expression and protein translation and how these changes alter brain development.
2023-06-21 | GSE227891 | GEO
Project description:Glial cells are central players in the pathogenesis of neurodevelopmental disorders like Fetal Alcohol Spectrum Disorder (FASD). Ethanol can modulate glial differentiation and astrocyte function imposing dramatic changes to the developing brain. Since ethanol can affect a vast number of intracellular targets and signaling pathways and many effects of early alcohol exposure on cell physiology can persist into adulthood, we tested the hypothesis that ethanol exposure in ferrets during a period equivalent to the last months of human gestation leads to a long-lasting change in astrocyte secretome in vitro. Animals were treated every other day with ethanol (5g/kg) or saline between post-natal day (P)10-30. At P31, astrocyte cultures were made and cells were submitted to stable isotope labeling by amino acids (SILAC). 24h-conditioned media of cells obtained from ethanol- or saline-treated animals (ET-CM or SAL-CM) were collected and analyzed by quantitative mass spectrometry in tandem with liquid chromatography. Here we show that 65 out of 280 quantifiable proteins displayed significant differences comparing ET-CM to SAL-CM. Among 59 proteins found reduced in ET-CM we found components of the extracellular matrix like Laminin subunits α2, α4, β1, β2 and γ1 and the proteoglycans Biglycan, Heparin Sulfate Proteoglycan 2 and Lumican. Proteins with trophic function like Insulin-Like Growth Factor Binding Protein 4, Pigment Epithelium-Derived Factor and Clusterin as well as proteins involved on modulation of proteolysis like TIMP-1 and PAI-1 were also found reduced. On the other hand, pro-synaptogeneic proteins like Thrombospondin-1, Hevin as well as the modulator of extracelular matrix expression, Angiotensinogen, were found increased in ET-CM. The analysis of interactome maps through Ingenuity Pathway Analysis demonstrated that the Amyloid beta A4 protein precursor (APP), which was found reduced in ET-CM, was previously shown to interact with ten other proteins that exhibited significant changes in the ET-CM, rendering it a suitable target for a more accurate analysis about the effects of ethanol on its biology. Taken together our results strongly suggest that early exposure to teratogens such alcohol may lead to an enduring change in astrocyte secretome, affecting mainly the expression of trophic and matricellular proteins, which in turn may lead to permanent alterations in brain function.
2016-02-15 | PXD002787 | Pride
Project description:Inflammation features in diverse central nervous system disorders such as stroke, trauma, neurodegeneration, infection and autoimmunity. To better understand how inflammatory mediators may alter astrocyte functions, we examined the effects of transforming growth factor-β1 (TGF-β1), lipopolysaccharide (LPS) and interferon-gamma (IFNγ) on purified, murine, primary cortical astrocyte cultures. We used microarrays to conduct whole genome expression profiling, and measured calcium signaling, which is implicated in mediating dynamic astrocyte functions. Combinatorial exposure to TGF-β1, LPS and IFNγ significantly modulated astrocyte expression of over 6,800 genes and resulted in both additive and synergistic changes compared with individual stimuli alone. Bioinformatic analysis revealed that combinatorial treatment significantly and markedly up regulated molecular networks and pathways associated with immune signaling and with regulation of cell compromise, death, growth and proliferation. These findings provide databases of astrocyte transcriptome changes elicited by the inflammatory stimuli, TGF-β1, LPS and IFNγ alone and in combination, and show that these stimuli up regulate astrocyte molecular networks associated with immune- and injury-related functions and significantly alter astrocyte calcium signaling evoked by multiple GPCR.
2012-10-18 | GSE36089 | GEO
Project description:Purpose: Traditional whole-tissue sequencing approaches do not fully capture brain cell-type specific effects of chronic alcohol. Therefore, the purpose of this study was to identify the specific transcriptome alterations in astrocytes due to chronic alcohol. Methods: We performed RNA-sequencing on astrocytes isolated from the prefrontal cortex (PFC) of C57BL/6J mice following chronic every-other-day alcohol consumption. Results: Differential expression analysis revealed alcohol-induced gene expression changes unique to astrocytes that could not be identified using whole tissue homogenate analysis. Enrichment analysis revealed involvement of calcium-related signaling and regulation of extracellular matrix genes in the astrocyte response to alcohol abuse. Conclusion: Our study presents the first focused analysis on the astrocyte transcriptome following chronic alcohol consumption, provides a framework for studying the functional response of astrocytes to alcohol and the possible astrocyte-specific effects of alcohol. In addition, our data represents a novel resource for groups interested in biological functions of astrocytes in the adult mouse PFC.
2018-01-10 | GSE92457 | GEO
Project description:Background: Fetal Alcohol Spectrum Disorders (FASD) cause life-long cognitive and behavioral impairment and are highly prevalent across the world. The effects of developmental ethanol exposure on astrocyte functions in vivo are poorly understood. To fill this gap, we assessed changes in the astrocyte translatome following in vivo developmental ethanol exposure and mechanistically linked some of these changes to altered neuronal development. Methods: The translating RNA from hippocampal astrocytes of neonatal Aldh1l1-EGFP-Rpl10a mice exposed to ethanol was isolated by Translating Ribosomal Affinity Purification and sequenced; neuronal dendritic morphology was assessed by Golgi-Cox staining and morphometric analysis; chondroitin sulfate glycosaminoglycan (CS-GAG) disaccharides were measured by Liquid Chromatography/Mass Spectrometry; neurite outgrowth was assessed in in vitro hippocampal neurons incubated in the presence of astrocyte-conditioned medium prepared from control and Chpf2-silenced astrocytes. Results: Translatome results suggested that ethanol alters mechanisms of astrocyte-neuron interactions involved in neuronal development. Moreover, ethanol increased dendritic arborization in hippocampal pyramidal neurons, inhibited the astrocyte translation of enzymes involved in the biosynthesis of inhibitory CS-GAGs, and decreased the levels of disaccharides forming CS-GAGs in vivo. Lastly, the silencing of CS-GAG biosynthetic enzyme Chpf2 in astrocyte cultures increased neurite branching of hippocampal neuron in vitro. Conclusions: Translatome analysis revealed novel effects of developmental ethanol exposure on astrocytes and provided mechanistic insights into altered brain development possibly relevant to the pathophysiology of FASD. We also identified a novel mechanism by which ethanol-induced reduction of astrocyte-produced inhibitory extracellular matrix components CS-GAGs increases dendritic arborization.
2024-09-30 | GSE272272 | GEO
Project description:Astrocytes play a critical role in brain function, but their contribution during ethanol (EtOH) consumption remains largely understudied. In light of recent findings on the heterogeneity of astrocyte physiology and gene expression, an approach with the ability to identify subtypes and capture this heterogeneity is necessary. Here, we combined measurements of calcium signaling and gene expression to define EtOH-induced astrocyte subtypes. In the absence of a demonstrated EtOH receptor, EtOH is believed to have effects on the function of many receptors and downstream biological cascades that underlie calcium responsiveness. This mechanism of EtOH-induced calcium signaling is unknown and this study provides the first step in understanding the characteristics of cells displaying these observed responses. To characterize underlying astrocyte subtypes, we assessed the correlation between calcium signaling and astrocyte gene expression signature in response to EtOH. We found that various EtOH doses increased intracellular calcium levels in a subset of astrocytes, distinguishing three cellular response types and one nonresponsive subtype as categorized by response waveform properties. Furthermore, single-cell RNA-seq analysis of astrocytes from the different response types identified type-enriched discriminatory gene expression signatures. Combining single-cell calcium responses and gene expression analysis identified specific astrocyte subgroups among astrocyte populations defined by their response to EtOH. This result provides a basis for identifying the relationship between astrocyte susceptibility to EtOH and corresponding measurable markers of calcium signaling and gene expression, which will be useful to investigate potential subgroup-specific influences of astrocytes on the physiology and pathology of EtOH exposure in the brain.
| S-EPMC9293641 | biostudies-literature
Project description:In this study, we generated knock-in CalExflox mice (Calcium Extrusion) for Cre-dependent expression of mCherry-hPMCA2w/b to attenuate astrocyte calcium signaling in genetically defined cells in vivo. We crossed CalExflox mice to astrocyte specific Aldh1l1-Cre/ERT2 mice in order to achieve inducible global CNS-wide calicum signaling attenuation. Within six days of induction in the bigenic mice, we observed profoundly altered ambulation in the open field, disrupted motor coordination and gait, and premature lethality, which based on imaging, behavioural, and RNA-seq analyses was likely to be partly due to significant cerebellar defects.
2021-07-14 | GSE164235 | GEO
Project description:Ethanol induced transcriptional and translational changes in Aldh1l1-EGFP/Rpl10a cortical astrocyte cultures
| PRJNA947241 | ENA