Mus musculus
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ABSTRACT:
PROVIDER: PRJNA121769 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Goal of the experiment: Analysis of gene expression changes in the cortex, striatum, hippocampus, hypothalamus, Drd2-MSNs and Drd1-MSNs of mice with a postnatal, neuron-specific ablation of GLP or G9a as compared to control mice. For microarray analysis, hippocampus, hypothalamus, cortex and striatum of Camk2a-Cre; GLPfl/fl, Camk2a-Cre; G9afl/fl and age (10-14 week old) and sex matched littermate controls were used for total RNA purification. Four biological replicates were performed for each experiment. Polyribosome associated mRNAs from five, age (10-14 week old) and sex matched Drd1-Cre; Drd1-bacTRAP; G9afl/fl, or Drd2-Cre; Drd2-bacTRAP; G9afl/fl and Drd1-bacTRAP; G9afl/fl or Drd2-bacTRAP; G9afl/fl control mice were used. Three biological replicates were performed for each experiment.
2009-12-10 | E-GEOD-19402 | biostudies-arrayexpress
Project description:Goal of the experiment: Analysis of gene expression changes in the cortex, striatum, hippocampus, hypothalamus, Drd2-MSNs and Drd1-MSNs of mice with a postnatal, neuron-specific ablation of GLP or G9a as compared to control mice.
2009-12-10 | GSE19402 | GEO
Project description:A more complete understanding of the molecular mechanisms by which substance use is encoded in the brain could illuminate novel strategies to treat substance use disorders, including cocaine use disorder (CUD). We have previously discovered that Zfp189, which encodes a Krüppel-associated box zinc finger protein (KZFP) transcription factor (TF), differentially accumulates in nucleus accumbens (NAc) Drd1+ and Drd2+ medium spiny neurons (MSNs) over the course of cocaine exposure and is causal in producing MSN functional and behavioral changes to cocaine. Here, we aimed to illuminate the brain cell-type specific molecular mechanisms through which this KZFP TF produces chronic cocaine -related brain changes, with emphasis on investigating transposable elements (TEs), since KZFPs like ZFP189 are known regulators of TEs. We discovered that expression of NAc TE transcripts was dramatically increased by cocaine experience, the most sensitive NAc cell-type was MSNs, and TEs in Drd1+ MSNs were considerably more dynamic over the course of cocaine exposure than TEs in Drd2+ MSNs. We demonstrated that synthetic ZFP189VPR is capable of dysregulating NAc TEs. In our snRNAseq data we observed that, relative to ZFP189WT, NAc manipulated with ZFP189VPR impeded cocaine-induced gene expression in NAc cell-types, including both Drd1+ and Drd2+ MSNs. Within either MSN subtype, the consequence of normal ZFP189 function was to enhance immune-related gene expression, and ZFP189VPR impeded these gene expression profiles. We discovered that behavioral and cell morphological adaptations to cocaine are produced by dysregulating TEs with ZFP189VPR in Drd1+ MSNs or stabilizing TEs with ZFP189WT in Drd2+ MSNs, revealing a persistent opponent process balanced across MSN subtypes and weighted by TE stability and consequent gene expression within MSN subtype.
2025-08-27 | GSE296548 | GEO
Project description:A more complete understanding of the molecular mechanisms by which substance use is encoded in the brain could illuminate novel strategies to treat substance use disorders, including cocaine use disorder (CUD). We have previously discovered that Zfp189, which encodes a Krüppel-associated box zinc finger protein (KZFP) transcription factor (TF), differentially accumulates in nucleus accumbens (NAc) Drd1+ and Drd2+ medium spiny neurons (MSNs) over the course of cocaine exposure and is causal in producing MSN functional and behavioral changes to cocaine. Here, we aimed to illuminate the brain cell-type specific molecular mechanisms through which this KZFP TF produces chronic cocaine -related brain changes, with emphasis on investigating transposable elements (TEs), since KZFPs like ZFP189 are known regulators of TEs. We discovered that expression of NAc TE transcripts was dramatically increased by cocaine experience, the most sensitive NAc cell-type was MSNs, and TEs in Drd1+ MSNs were considerably more dynamic over the course of cocaine exposure than TEs in Drd2+ MSNs. We demonstrated that synthetic ZFP189VPR is capable of dysregulating NAc TEs. In our snRNAseq data we observed that, relative to ZFP189WT, NAc manipulated with ZFP189VPR impeded cocaine-induced gene expression in NAc cell-types, including both Drd1+ and Drd2+ MSNs. Within either MSN subtype, the consequence of normal ZFP189 function was to enhance immune-related gene expression, and ZFP189VPR impeded these gene expression profiles. We discovered that behavioral and cell morphological adaptations to cocaine are produced by dysregulating TEs with ZFP189VPR in Drd1+ MSNs or stabilizing TEs with ZFP189WT in Drd2+ MSNs, revealing a persistent opponent process balanced across MSN subtypes and weighted by TE stability and consequent gene expression within MSN subtype.
2025-08-27 | GSE296397 | GEO
Project description:Cocaine-mediated repression of the histone methyltransferase (HMT) G9a has recently been implicated in transcriptional, morphological, and behavioral responses to chronic cocaine administration. Here, using a ribosomal affinity purification approach, we find that G9a repression by cocaine occurs in both Drd1 (striatonigral)- and Drd2 (striatopallidal)-expressing medium spiny neurons (MSNs). Conditional knockout and overexpression of G9a within these distinct cell types, however, reveals divergent behavioral phenotypes in response to repeated cocaine treatment. Our studies further indicate that such developmental deletion of G9a selectively in Drd2 neurons results in the unsilencing of transcriptional programs normally specific to striatonigral neurons, and the acquisition of Drd1-associated projection and electrophysiological properties. This partial striatopallidal to striatonigral ‘switching’ phenotype in mice indicates a novel role for G9a in contributing to neuronal subtype identity, and suggests a critical function for cell-type specific histone methylation patterns in the regulation of behavioral responses to environmental stimuli. Polyribosome associated mRNAs from 2-5 month old, age and sex matched Drd1-Cre; Drd1-TRAP; G9afl/fl and Drd1-TRAP; G9afl/fl, Drd2-Cre; Drd2-TRAP; G9afl/fl and Drd2-TRAP; G9afl/fl mice (n = 2-4 mice/genotype/drug treatment, 2 hours after the last of eight repeated cocaine injections of 20 mg/kg/day) were obtained as previously described. EGFP labeled ribosomes and associated mRNAs were immunoprecipitated using a mix of two monoclonal anti-GFP antibodies (50 μg of clones #19C8 and #19F7 for each IP, available at Sloan-Kettering Monoclonal Antibody Facility). Purified mRNA was amplified and processed for microarray and qPCR analysis using the Affymetrix two-cycle cDNA Synthesis kit (Affymetrix) as previously described. Affymetrix Mouse Genome 430 2.0 arrays were used in all experiments. Information regarding the array design and features can be found at www.affymetrix.com. Mouse Genome 430 2.0 arrays were scanned using the GeneChip Scanner 3000 (Affymetrix) and globally scaled to 150 using the Affymetrix GeneChip Operating Software (GCOS v1.4).
2014-02-05 | E-GEOD-54656 | biostudies-arrayexpress
Project description:We profiled genome-wide gene expression across four brain regions (hippocampus, prefrontal cortex, striatum, and hypothalamus) in male and female C57BL/6NTac mice using a perinatal morphine exposure model of Neonatal Opioid Withdrawal Syndrome (NOWS). Mice received morphine or saline perinatally, then were challenged with LPS or saline in adulthood, yielding four groups (SAL-SAL, SAL-LPS, MOR-SAL, MOR-LPS). NeuN+ neuronal nuclei (~5,000 per sample) were isolated by FACS from PFC, hippocampus, hypothalamus, and striatum and profiled by RNA-seq (Illumina NovaSeq X Plus, paired-end 150 bp). RNA-seq identified differentially expressed genes enriched in immune and metabolic pathways, with the hypothalamus displaying the most pronounced transcriptional response to perinatal morphine exposure.
2026-06-17 | GSE332798 | GEO
Project description:We report single-nucleus transcriptomes from brain regions in 5 species: mice: Frontal Cortex, V1, Hippocampus, Striatum; common marmoset: 7 neocortical regions, Hippocampus, Striatum (Nucleus Accumbens, Caudate, Putamen); rhesus macaque: Prefrontal Cortex, V1; human: Prefrontal Cortex, V1, Striatum (Caudate); ferret: Prefrontal Cortex, V1, Striatum
2020-06-04 | GSE151761 | GEO
Project description:Cocaine-mediated repression of the histone methyltransferase (HMT) G9a has recently been implicated in transcriptional, morphological, and behavioral responses to chronic cocaine administration. Here, using a ribosomal affinity purification approach, we find that G9a repression by cocaine occurs in both Drd1 (striatonigral)- and Drd2 (striatopallidal)-expressing medium spiny neurons (MSNs). Conditional knockout and overexpression of G9a within these distinct cell types, however, reveals divergent behavioral phenotypes in response to repeated cocaine treatment. Our studies further indicate that such developmental deletion of G9a selectively in Drd2 neurons results in the unsilencing of transcriptional programs normally specific to striatonigral neurons, and the acquisition of Drd1-associated projection and electrophysiological properties. This partial striatopallidal to striatonigral ‘switching’ phenotype in mice indicates a novel role for G9a in contributing to neuronal subtype identity, and suggests a critical function for cell-type specific histone methylation patterns in the regulation of behavioral responses to environmental stimuli.
2014-02-05 | GSE54656 | GEO
Project description:Understanding the molecular mechanisms driving selective neuronal vulnerability to different neurodegenerative disorders remains a crucial, but unsolved question. Here we explored the case of Huntington's disease (HD), where the striatum and, specifically, dopamine receptor 1 (D1R) and dopamine receptor 2 (D2R) medium-sized spiny neurons (MSNs), exhibit differential susceptibility to the HTT CAG-repeat expansion mutation, with D2R-neurons being impacted earlier and more significantly. To unravel differences between D2R and D1R MSNs, we employed a multidimensional approach, integrating genomic, transcriptional, morphological, and somatic instability analyses. Specifically, we used Htt CAG knock-in mouse models harboring 18 (HttQ20: “control”) or ~190 (HttQ175: “HD”) consecutive CAG repeats, expressing tdTomato and EGFP under the control of Drd1 and Drd2 promoters, respectively. First, comprehensive genomic and transcriptomic analyses following fluorescence-activated cell sorting of dissociated striatal neurons, revealed no large copy number variations, but distinct gene expression profiles, indicating a significant upregulation of oxidative phosphorylation and translation pathways in D1R positive neurons at pre-symptomatic stage. Secondly, morphological analyses revealed a greater proportion of D1R-positive neurons compared to D2R-positive neurons in HD mice, particularly in the ventral-medial striatum, with D2R-positive neurons presenting an increased nuclear accumulation of mutant huntingtin aggregates. In summary, our integrative study suggests that the distinct vulnerability of MSNs in HD might result from a combination of an early transcriptional compensatory/buffering-response of D1R neurons together with specific susceptibility of D2R neurons.
2026-08-31 | GSE307772 | GEO
Project description:Understanding the molecular mechanisms driving selective neuronal vulnerability to different neurodegenerative disorders remains a crucial, but unsolved question. Here we explored the case of Huntington's disease (HD), where the striatum and, specifically, dopamine receptor 1 (D1R) and dopamine receptor 2 (D2R) medium-sized spiny neurons (MSNs), exhibit differential susceptibility to the HTT CAG-repeat expansion mutation, with D2R-neurons being impacted earlier and more significantly. To unravel differences between D2R and D1R MSNs, we employed a multidimensional approach, integrating genomic, transcriptional, morphological, and somatic instability analyses. Specifically, we used Htt CAG knock-in mouse models harboring 18 (HttQ20: “control”) or ~190 (HttQ175: “HD”) consecutive CAG repeats, expressing tdTomato and EGFP under the control of Drd1 and Drd2 promoters, respectively. First, comprehensive genomic and transcriptomic analyses following fluorescence-activated cell sorting of dissociated striatal neurons, revealed no large copy number variations, but distinct gene expression profiles, indicating a significant upregulation of oxidative phosphorylation and translation pathways in D1R positive neurons at pre-symptomatic stage. Secondly, morphological analyses revealed a greater proportion of D1R-positive neurons compared to D2R-positive neurons in HD mice, particularly in the ventral-medial striatum, with D2R-positive neurons presenting an increased nuclear accumulation of mutant huntingtin aggregates. In summary, our integrative study suggests that the distinct vulnerability of MSNs in HD might result from a combination of an early transcriptional compensatory/buffering-response of D1R neurons together with specific susceptibility of D2R neurons.
2026-08-31 | GSE307771 | GEO