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RNA-seq of brain and sperm and Bisulfite-seq of embryos from normal and stress-induced depressed mice

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE133498 | GEO | 2020/06/28

REPOSITORIES: GEO

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RNA-seq of brain and sperm and Bisulfite-seq of embryos from normal and stress-induced depressed mice

Project description:RNA-seq of brain and sperm and Bisulfite-seq of embryos from normal and stress-induced depressed mice

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Genome-wide bisulfite sequencing of embryos at E4.5 stage injected with sRNAs from normal and stress-induced depressed mice

Project description:We demonstrated that DNMT3a was decreased at E3.5 to E6.5 stage in embryos developing from zygotes injected with sperm sRNAs from depressed mice.To uncover the consequence caused by DNMT3a transient reduction in developing embryos, we injected sperm sRNAs from normal or depressed mice into zygotes and systematically profiled the DNA methylome of embryos at E4.5 stage (sRNA-Dep-E4.5 vs sRNA-Ctl-E4.5) by single-cell level whole genome bisulphite sequencing (SC-WGBS).

2020-06-28 | GSE133496 | GEO

Genome-wide bisulfite sequencing of embryos at E4.5 stage injected with sRNAs from normal and stress-induced depressed mice

Project description:Genome-wide bisulfite sequencing of embryos at E4.5 stage injected with sRNAs from normal and stress-induced depressed mice

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RNA sequencing of hippocampal sample from normal male mice, stress induced depressive male mice and male offspring born to stress-induced depressed male mice

Project description:We demonstrated that the offspring of depressed fathers display reduced resilience to stress and enhanced susceptibility to depression. To explain the observed behavioural phenotypes of depression in offspring produced by depressed fathers, molecular profiling was performed in key brain regions.We examined the hippocampal sample from normal male mice, stress induced depressive male mice and male offspring born to stress-induced depressed male mice by RNA sequencing.

2020-06-28 | GSE133494 | GEO

Small RNA sequencing of sperm sample from normal or stress induced depressive male mice

Project description:We demonstrated that sperm sRNAs are sufficient to reproduce the effect of sperm RNAs on inducing depressive symptoms in offspring.To identify the specific subtypes of sperm sRNAs that cause abnormalities in offspring, we examined the sRNA profiles of sperm derived from normal or depressed male mice by RNA deep sequencing.

2020-06-28 | GSE133497 | GEO

Integrative Analyses of scRNA-seq, Bulk mRNA-seq, and DNA Methylation Profiling in Depressed Suicide Brain Tissues.

Project description:BackgroundSuicidal behaviors have become a serious public health concern globally due to the economic and human cost of suicidal behavior to individuals, families, communities, and society. However, the underlying etiology and biological mechanism of suicidal behavior remains poorly understood.MethodsWe collected different single omic data, including single-cell RNA sequencing (scRNA-seq), bulk mRNA-seq, DNA methylation microarrays from the cortex of Major Depressive Disorder (MDD) in suicide subjects' studies, as well as fluoxetine-treated rats brains. We matched subject IDs that overlapped between the transcriptome dataset and the methylation dataset. The differential expression genes and differentially methylated regions were calculated with a 2-group comparison analysis. Cross-omics analysis was performed to calculate the correlation between the methylated and transcript levels of differentially methylated CpG sites and mapped transcripts. Additionally, we performed a deconvolution analysis for bulk mRNA-seq and DNA methylation profiling with scRNA-seq as the reference profiles.ResultsDifference in cell type proportions among 7 cell types. Meanwhile, our analysis of single-cell sequence from the antidepressant-treated rats found that drug-specific differential expression genes were enriched into biological pathways, including ion channels and glutamatergic receptors.ConclusionsThis study identified some important dysregulated genes influenced by DNA methylation in 2 brain regions of depression and suicide patients. Interestingly, we found that oligodendrocyte precursor cells (OPCs) have the most contributors for cell-type proportions related to differential expression genes and methylated sites in suicidal behavior.

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ChIP-seq protocol for sperm cells and embryos to assess environmental impacts and epigenetic inheritance.

Project description:In the field of epigenetic inheritance, delineating molecular mechanisms implicated in the transfer of paternal environmental conditions to descendants has been elusive. This protocol details how to track sperm chromatin intergenerationally. We describe mouse model design to probe chromatin states in single mouse sperm and techniques to assess pre-implantation embryo chromatin and gene expression. We place emphasis on how to obtain high-quality and quantifiable data sets in sperm and embryos, as well as highlight the limitations of working with low input. For complete details on the use and execution of this protocol, please refer to Lismer et al. (2021).

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Brain activation induced by chronic psychosocial stress in mice.

Project description:Chronic psychosocial stress is a well-established risk factor for neuropsychiatric diseases. Abnormalities in brain activity have been demonstrated in patients with stress-related disorders. Global brain activation patterns during chronic stress exposure are less well understood but may have strong modifying effects on specific brain circuits and thereby influence development of stress-related pathologies. We determined neural activation induced by chronic social defeat stress, a mouse model of psychosocial stress. To assess chronic activation with an unbiased brain-wide focus we used manganese-enhanced magnetic resonance imaging (MEMRI) and immunohistochemical staining of ∆FOSB, a transcription factor induced by repeated neural activity. One week after 10-day social defeat we observed significantly more activation in several brain regions known to regulate depressive and anxiety-like behaviour, including the prefrontal cortex, bed nucleus of stria terminalis, ventral hippocampus and periaqueductal grey in stressed compared to control mice. We further established that the correlation of ∆FOSB positive cells between specific brain regions was altered following chronic social defeat. Chronic activation of these neural circuits may relate to persistent brain activity changes occurring during chronic psychosocial stress exposure, with potential relevance for the development of anxiety and depression in humans.

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Hypothalamic Proteomics analysis of lipopolysaccharide (LPS)-induced depressed mice

Project description:Hypothalamic dysfunction is a key pathological factor in inflammation-associated depression. In the present study, isobaric tags for relative-absolute quantitation (iTRAQ) combined with mass spectrometry were employed to detect the proteomes in the hypothalamus of the lipopolysaccharide (LPS)-induced depression mouse. A total of 187 proteins were differentially expressed compared with the control group. The results indicated altered molecules were clustered into Ephrin receptor signalling; glutamatergic transmission, and inflammation-related signalling. Ephrin type-B receptor 2 (EPHB2), a transmembrane receptor protein in Ephrin receptor signalling, was significantly elevated and interacted with the accumulated NMDAR subunit GluN2A in the hypothalamus. Additionally, molecules involved in synaptic plasticity regulation, such as hypothalamic postsynaptic density protein-95 (PSD-95), p-AKT and brain-derived neurotrophic factor (BDNF), were significantly altered in the LPS-induced depressed group. It might be an underlying pathogenesis that the EPHB2-GluN2A-AKT cascade regulates synaptic plasticity in depression. EPHB2 can be a potential therapeutic target in the correction of glutamatergic transmission dysfunction. In summary, our findings point to the previously undiscovered molecular underpinnings of the pathophysiology in the hypothalamus of inflammation-associated depression and offer potential targets to develop antidepressants.

2020-01-09 | PXD016040 | Pride

RNA sequencing of hippocampal sample from normal male mice, stress induced depressive male mice and male offspring born to stress-induced depressed male mice

Project description:RNA sequencing of hippocampal sample from normal male mice, stress induced depressive male mice and male offspring born to stress-induced depressed male mice

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