Epigenomic and chromosomal architectural reconfiguration in developing human frontal cortex and hippocampus
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PROVIDER: PRJNA883388 | ENA |
REPOSITORIES: ENA
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Project description:Human frontal cortex and hippocampus play key roles in learning and cognition, and are representative structures of the six-layer neocortex and the more ancient allocortex, respectively. Here we investigated the epigenomic and 3D-chromatin conformational dynamics of human frontal cortex and hippocampus development using more than 53,000 joint single-nucleus profiles of chromatin conformation and DNA methylation (sn-m3C-seq) generated from mid-gestational, late-gestational, infant and adult human brains. We found that the remodeling of DNA methylation predominantly happens during late-gestational to early-post-natal development, and is temporally uncoupled from the dynamics of chromatin conformation. We reconstructed regulatory hierarchies of cortical and hippocampal cell differentiation and maturation and identified brain regional-specific regulatory signatures. The single-cell 3D-regulatome approach further enabled the cell-type-specific dissection of neuropsychiatric risk loci during key neurodevelopmental stages and in adult human brains.
2022-10-07 | GSE213950 | GEO
Project description:We used Affymetrix miRNA arrays to analyze the expression of miRNAs in the frontal cortex and hippocampus of 8-week-old C57BL/6J wt mice. We compared these microarray-based expression profiles to ones obtained by miRNA sequencing from the same brain regions of the same mouse strain. miRNA expression profiling of frontal cortex and hippocampus from C57BL/6J mice (N=3) was performed with Affymetrix miRNA array
2011-06-22 | E-GEOD-27891 | biostudies-arrayexpress
Project description:Microglia is dynamically reprogrammed according to the progression of Alzheimer’s disease (AD). However, clinical translation into biomarker development for functional change in microglia has not been achieved. Here, we find the close association of the metabolic reconfiguration of microglia with increased hippocampal glucose uptake, which can be noninvasively estimated by [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). We found that increased FDG activity in the hippocampus of an AD mouse model depended on microglial uptake. Single-cell RNA-sequencing of the hippocampus showed the changes of glucose metabolism profiles including glucose transporters, glycolysis and oxidative phosphorylation mainly occurred in microglia. A subset of microglia with high glucose transporters with defective glycolysis and oxidative phosphorylation was increased according to disease progression. Furthermore, we also found a positive association between a soluble TREM2 of cerebrospinal fluid, a marker of microglial activation, and hippocampal FDG uptake as a human study. We identified a reconfiguration of microglial glucose metabolism in the hippocampus of AD and suggested a feasible imaging biomarker based on widely used FDG PET to reflect microglial metabolic profiles.
2021-09-08 | GSE150934 | GEO
Project description:MicroRNAs (miRNAs) are small regulatory molecules that cause post-transcriptional gene silencing. Although some miRNAs are known to have region-specific expression patterns in the adult brain, the functional consequences of the region-specificity to the gene regulatory networks of the brain nuclei are not clear. Therefore, we studied miRNA expression patterns by miRNA-seq in two brain regions, frontal cortex (FCx) and hippocampus (HP), which have separate biological functions. We identified 354 miRNA from FCx and 408 from HP. Several miRNA families and clusters were differentially expressed between FCx and HP, including the miR-8 family, miR-182|miR-96|miR-183 cluster, and miR-212|miR-312 cluster overexpressed in FCx and miR-34 family overexpressed in HP. To visualize the clusters, we developed support for viewing genomic alignments of miRNA-seq reads in the Chipster genome browser. We carried out pathway analysis of the predicted target genes of differentially expressed miRNA families and clusters to assess their putative biological functions. Interestingly, specific pathways were identified that are predicted to be regulated by several miRNAs from the same family/cluster. We have developed a miRNA-seq approach with a bioinformatic analysis workflow that is suitable for studying miRNA expression patterns from specific brain nuclei. FCx and HP were shown to have distinct miRNA expression patterns which were reflected in the predicted gene regulatory pathways. This methodology can be applied for the identification of brain region-specific and phenotype-specific miRNA-mRNA-regulatory networks from the adult and developing rodent brain. miRNA-seq of 3 replicates from frontal cortex, 3 replicates from hippocampus, and pooled sequence runs from both
2011-06-21 | E-GEOD-27979 | biostudies-arrayexpress
Project description:Purpose: We carried out small RNA sequencing to determine miRNA expression patterns of hippocampus and frontal cortex in six inbred mouse strains. We analyzed miRNA expression levels, isomiR distribution and miRNA editing events. Methods: We constructed small RNA libraries starting from the total RNA extracted from the hippocampus and frontal cortex of three animals per strain. The sequencing was carried out using Illumina HiSeq2000 (single-end). The sequence reads that passed quality filters were mapped to the mouse genome (mm10) and to known miRNAs (miRBase v21) using miRDeep2, SeqBuster, and sRNAbench, to obtain miRNA and isomiR expression levels and to predict novel miRNAs. Genome alignments were analysed for miRNA editing using FreeBayes. Results: We detected significant miRNA and isomiR expression level differences between the strains and brain regions. Most of the miRNA loci produced a number of isomiRs. Some miRNAs were consistently edited with a pattern that matches the activity of known RNA editing enzymes.
2018-01-18 | GSE84408 | GEO
Project description:We used Affymetrix miRNA arrays to analyze the expression of miRNAs in the frontal cortex and hippocampus of 8-week-old C57BL/6J wt mice. We compared these microarray-based expression profiles to ones obtained by miRNA sequencing from the same brain regions of the same mouse strain.
2011-06-22 | GSE27891 | GEO
Project description:Objective: To elucidate the potential effects of stressful factors for depression on the hippocampal, frontal cortex and pituitary gland genome-wide transcriptomes at the molecular level, we evaluated the transcriptomic profiles of depression rats under chronic restraint stress (CRS). Methods: Forty-eight rats were randomly divided into control, model, fluoxetine and acupuncture groups. Experimental period was 28 days. Open-field test, Sucrose preference and body weight were investigated respectively at the experiment before and after the experiment. The experiment having been finished, solexa sequencing technology (Illumina Nextseq 500/151nt) was applied to investigate and verify the altered hippocampal, frontal cortex and pituitary gland genome-wide transcriptome analysis in rats of all groups. Results: Based on the data from RNA-seq analysis, it revealed that compared the expression of genes in the control group with model group in the respective of three brain tissues, 101, 134, 148 differential expression genes were found in the hippocampus, frontal cortex and pituitary gland, respectively; compared the expression of genes in the fluoxetine group with model group in the respective of three brain tissues, 41, 46, 87 differential expression genes were found in the hippocampus, frontal cortex and pituitary gland, respectively; compared the expression of genes in the acupuncture group with model group in the respective of three brain tissues, 107, 89, 179 differential expression genes were found in the hippocampus, frontal cortex and pituitary gland, respectively. Furthermore, we used the GO (Gene ontology) analysis and KEGG (Kyo-To conservation of Genes and Genomes) pathway analysis for these differentially expressed genes. We found that the results of these two analyses were consistent, both mainly related to monoamine neurotransmitters, inflammation and immune response in control group VS model group. It is noted that this phenomenon also appears in fluoxetine group compared with model group, acupuncture group VS model group. Importantly, the antidepressant effect of acupuncture was more extensive, which was more consistent with the pathogenesis of depression induced by CRS in rats. Conclusions: Our study represents the first detailed analysis of the hippocampal, frontal cortex and pituitary gland genome-wide transcriptomes in depression rats under CRS by RNA-seq technology. The results of this study revealed multiple DEGs and possible mechanisms specifying the function of hippocampal, frontal cortex and pituitary gland in depression rats induced by CRS. These results provide a basis for further investigation of the signaling mechanisms that affect central nervous system output related to stress-sensitive depressive disorder development.
2017-09-24 | GSE86392 | GEO
Project description:Increased glucose uptake in hippocampus as a surrogate biomarker of metabolic reconfiguration of microglia in Alzheimer’s disease
| PRJNA634112 | ENA
Project description:Transcribed regions in adult temporal lobe, hippocampus and frontal lobe were assesed by strand specific next generation sequencing of polyA RNA.
2014-09-01 | GSE45910 | GEO
Project description:Detailed analysis of estrogen mediated enhancer landscape and chromosomal architectural changes specifically in human chromosome 21.
2019-02-10 | GSE99541 | GEO