Developmental Regulation and Individual Differences of Neuronal Epigenomes in the Prefrontal Cortex
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE21172 | GEO | 2010/04/20
SECONDARY ACCESSION(S): PRJNA125799
REPOSITORIES: GEO
Similar Datasets
Project description:We report global distribution of trimethylated Histone H3 Lysine 4 (H3K4me3) in human prefrontal cortex neurons at different ages Neuronal nuclei from human prefrontal cortex were isolated by FACS. Regions marked by H3K4me3 were identified by chromatin immunoprecipiation followed by deep sequencing.
2010-04-20 | E-GEOD-21172 | biostudies-arrayexpress
Project description:Little is known about the regulation of neuronal and other cell-type specific epigenomes from the brain. Here, we map the genome-wide distribution of trimethylated histone H3K4 (H3K4me3), a mark associated with transcriptional regulation, in neuronal and nonneuronal nuclei collected from prefrontal cortex (PFC) of 11 individuals ranging in age from 0.5 to 69 years. Massively parallel sequencing identified 12,732-19,704 H3K4me3 enriched regions (peaks), the majority located proximal to (within 2 kb of) the transcription start site (TSS) of annotated genes. These included peaks shared by neurons in comparison with three control (lymphocyte) cell types, as well as peaks specific to individual subjects. We identified 6,213 genes that show highly enriched H3K4me3 in neurons versus control. At least 1,370 loci, including annotated genes and novel transcripts, were selectively tagged with H3K4me3 in neuronal but not in nonneuronal PFC chromatin. Our results reveal age-correlated neuronal epigenome reorganization, including decreased H3K4me3 at approximately 600 genes (many function in developmental processes) during the first year after birth. In comparison, the epigenome of aging (>60 years) PFC neurons showed less extensive changes, including increased H3K4me3 at 100 genes. These findings demonstrate that H3K4me3 in human PFC is highly regulated in a cell type- and subject-specific manner and highlight the importance of early childhood for developmentally regulated chromatin remodeling in prefrontal neurons.
| S-EPMC2889328 | biostudies-literature
Project description:78 tissue samples from prefrontal cortex (PFC) in human and macaque The data from human and macaque PFC samples with different ages were used to estimate gene expression changes, including both protein-coding genes and lincRNAs, in PFC along lifespan in the two species.
2014-05-14 | E-GEOD-51264 | biostudies-arrayexpress
Project description:How do individuals decide to act based on a rewarding status quo versus an unexplored choice that might yield a better outcome? Recent evidence suggests that individuals may strategically explore as a function of the relative uncertainty about the expected value of options. However, the neural mechanisms supporting uncertainty-driven exploration remain underspecified. The present fMRI study scanned a reinforcement learning task in which participants stop a rotating clock hand in order to win points. Reward schedules were such that expected value could increase, decrease, or remain constant with respect to time. We fit several mathematical models to subject behavior to generate trial-by-trial estimates of exploration as a function of relative uncertainty. These estimates were used to analyze our fMRI data. Results indicate that rostrolateral prefrontal cortex tracks trial-by-trial changes in relative uncertainty, and this pattern distinguished individuals who rely on relative uncertainty for their exploratory decisions versus those who do not.
| S-EPMC3285405 | biostudies-literature
Project description:To unravel the gene expression changes during postnatal prefrontal cortex development, RNA-seq was performed in the rat medial prefrontal cortex at five time points from early life to adulthood (postnatal day 8, 14, 21, 35 and 70) and differential expression of protein-coding genes, lincRNAs and alternative exons was analyzed. A switch from neuronal network development to maintenance during postnatal rat prefrontal cortex development was shown.
2017-01-01 | GSE79860 | GEO
Project description:The prefrontal cortex is greatly associated with a wide range of mental health illnesses including schizophrenia, depression, bipolar disorder, anxiety and autism spectrum disorders. It richly expresses neuroreceptors which are the target for typical and atypical antipsychotics. However as the precise mechanism of action of antipsychotic medications are not known, proteomic studies of the effects of antipsychotic drugs on the brain are warranted. In the current study we aimed to characterise protein expression in the adult rodent prefrontal cortex (n=5 per group) following low dose treatment with the atypical antipsychotic Risperidone or saline (control) in adolescence (postnatal days 34-47). The prefrontal cortex was examined by triplicate one hour runs of label-free LC-MS/MS. The raw mass spectral data were analyzed with the MaxQuantTM software. Statistical analysis was carried out using SAS Version 9.1. Functional and pathway analysis was performed with DAVID.nih and Ingenuity Pathway Analysis respectively and the top five most implicated pathways were found to be clathrin mediated endocytosis, the tri cyclic acid cycle, remodelling of epithelial junctions, rho family GTPase signalling and mitochondrial dysfunction.This brief report summarises the proteomic data obtained from the study described, adds to the current repertoire of data available concerning the effects of atypical antipsychotic drugs on the brain and sheds light on their biological mechanisms.
2014-05-13 | PXD000480 | Pride
Project description:In order to gain a global molecular perspective on how the human genome gives rise to the brain, we explore the temporal dynamics and genetic control of transcription in human dorsolateral prefrontal cortex in an extensive series of brain tissue from fetal development through aging. We discover a wave of gene expression changes occurring during fetal development which are reversed in early postnatal life. One half century later in life, this phenomenon is mirrored in aging as well as neurodegeneration. While we identify thousands of robust associations of individual genetic polymorphisms with gene expression, we also demonstrate that there is no association between the total extent of genetic differences between subjects and the global similarity of their transcriptional profiles. Hence, the human genome produces a consistent molecular architecture in the prefrontal cortex, despite millions of genetic differences across individuals and races. To enable further discovery, this entire dataset is freely available (GEO). RNA from 269 human prefrontal cortex samples ranging from fetal development (negative ages) through aging (80 years) were analyzed on custom 2-color microarrays from the National Human Genome Research Institute (NHGRI) microarray core facility using a reference RNA comprised of a pool of all samples. SNP genotype data for these subjects can be found in dbGAP under Study ID *phs000417.v1.p1* http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000417.v1.p1 Both the gene expression and SNP data from this study can be interrogated gene-by-gene with a biologist-friendly stand-alone application available at http://www.libd.org/braincloud . The original publication of this data appeared in the Oct. 27th 2011 volume of Nature: http://www.nature.com/nature/journal/v478/n7370/full/nature10524.html .
2011-10-26 | E-GEOD-30272 | biostudies-arrayexpress
Project description:Control processes allow us to constrain the retrieval of semantic information from long-term memory so that it is appropriate for the task or context. Control demands are influenced by the strength of the target information itself and by the circumstances in which it is retrieved, with more control needed when relatively weak aspects of knowledge are required and after the sustained retrieval of related concepts. To investigate the neurocognitive basis of individual differences in these aspects of semantic control, we used resting-state fMRI to characterise the intrinsic connectivity of left ventrolateral prefrontal cortex (VLPFC), implicated in controlled retrieval, and examined associations on a paced serial semantic task, in which participants were asked to detect category members amongst distractors. This task manipulated both the strength of target associations and the requirement to sustain retrieval within a narrow semantic category over time. We found that individuals with stronger connectivity between VLPFC and medial prefrontal cortex within the default mode network (DMN) showed better retrieval of strong associations (which are thought to be recalled more automatically). Stronger connectivity between the same VLPFC seed and another DMN region in medial parietal cortex was associated with larger declines in retrieval over the course of the category. In contrast, participants with stronger connectivity between VLPFC and cognitive control regions within the ventral attention network (VAN) had better controlled retrieval of weak associations and were better able to sustain their comprehension throughout the category. These effects overlapped in left insular cortex within the VAN, indicating that a common pattern of connectivity is associated with different aspects of controlled semantic retrieval induced by both the structure of long-term knowledge and the sustained retrieval of related information.
| S-EPMC8784820 | biostudies-literature
Project description:We used a chronic mild stress (CMS) protocol to separate susceptible-depression, susceptible-anxiety and insusceptible rat subgroups. Differential proteomes in the prefrontal cortex were analyzed based on isobaric tags for relative and absolute quantitation (iTRAQ) labeling combined with mass spectrometry.
2020-10-16 | PXD022045 |
Project description:To understand the roles of molecules in functional differentiation among adult human tissues, we performed a systematic survey of mRNA, protein, and protein phosphorylation as well as miRNA expression, in three tissues: cerebellum, prefrontal cortex and liver. We found that tissues were clearly distinct from one another at all levels. Furthermore, our results showed that miRNA differently expressed between tissues have significant, but modest effect on expression of mRNA and somewhat stronger effect on expression of proteins among the tissues. Notably, miRNA preferentially targeted gene regulators, transcription factors and kinases, in all three tissues studied. Following this path, we found that miRNA effect was further amplified through expression changes of target transcription factors and kinases, leading to further changes in their targets’ expression and phosphorylation levels. Importantly, miRNA regulation leads to reduced, rather than increased gene expression variation among individuals between two brain regions. These observations uncover the complexity of miRNA regulatory interactions and are compatible with suggested role of miRNA in gene expression canalization. Adult human post-mortem tissue samples: cerebellum, prefrontal cortex and liver, were collected. Each tissue contains three individuals totalling 9 samples in this datasets. RNA extracted from these dissected tissue was hybridized to Agilent Human miRNA Microarray.
2013-01-04 | E-GEOD-19505 | biostudies-arrayexpress