Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide maps of chromatin state in medium spiny neurons in the striatum of adult mice

ABSTRACT: Normal brain function critically depends on the interaction between highly specialized neurons that operate within anatomically and functionally distinct brain regions. The fidelity of neuronal specification is contingent upon the robustness of the transcriptional program that supports the neuron type-specific patterns of gene expression. Changes in neuron type-specific gene expression are commonly associated with neurodegenerative disorders including Huntington’s and Alzheimer’s disease. The neuronal specification is driven by gene expression programs that are established during early stages of neuronal development and remain in place in the adult brain. Here we show that the Polycomb repressive complex 2 (PRC2), which supports neuron specification during early differentiation, contributes to the suppression of the transcription program that can be detrimental for the adult neuron function. We show that PRC2 deficiency in adult striatal neurons and in cerebellar Purkinje cells impairs the maintenance of neuron-type specific gene expression. The deficiency in PRC2 has a direct impact on a selected group of genes that is dominated by self-regulating transcription factors normally suppressed in these neurons. The age-dependent progressive transcriptional changes in PRC2-deficient neurons are associated with impaired neuronal function and survival and lead to the development of fatal neurodegenerative disorders in mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE84244 | GEO | 2016/07/29

SECONDARY ACCESSION(S): PRJNA328469

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Genome-wide maps of chromatin state in medium spiny neurons in the striatum of adult mice

Project description:Normal brain function critically depends on the interaction between highly specialized neurons that operate within anatomically and functionally distinct brain regions. The fidelity of neuronal specification is contingent upon the robustness of the transcriptional program that supports the neuron type-specific patterns of gene expression. Changes in neuron type-specific gene expression are commonly associated with neurodegenerative disorders including Huntingtonâs and Alzheimerâs disease. The neuronal specification is driven by gene expression programs that are established during early stages of neuronal development and remain in place in the adult brain. Here we show that the Polycomb repressive complex 2 (PRC2), which supports neuron specification during early differentiation, contributes to the suppression of the transcription program that can be detrimental for the adult neuron function. We show that PRC2 deficiency in adult striatal neurons and in cerebellar Purkinje cells impairs the maintenance of neuron-type specific gene expression. The deficiency in PRC2 has a direct impact on a selected group of genes that is dominated by self-regulating transcription factors normally suppressed in these neurons. The age-dependent progressive transcriptional changes in PRC2-deficient neurons are associated with impaired neuronal function and survival and lead to the development of fatal neurodegenerative disorders in mice. Medium Spiny neuronal nuclei were isolated from adult mouse striata via NeuN-specific Flourescence Activated Nuclei Sorting.

2016-07-29 | E-GEOD-84244 | biostudies-arrayexpress

Microarray analysis of striatal tissue of wild type and Ezh1/Ezh2 dKO mice at 6 weeks, 3 months, and 6 months

Project description:Normal brain function critically depends on the interaction between highly specialized neurons that operate within anatomically and functionally distinct brain regions. The fidelity of neuronal specification is contingent upon the robustness of the transcriptional program that supports the neuron type-specific patterns of gene expression. Changes in neuron type-specific gene expression are commonly associated with neurodegenerative disorders including Huntingtonâ??s and Alzheimerâ??s disease. The neuronal specification is driven by gene expression programs that are established during early stages of neuronal development and remain in place in the adult brain. Here we show that the Polycomb repressive complex 2 (PRC2), which supports neuron specification during early differentiation, contributes to the suppression of the transcription program that can be detrimental for the adult neuron function. We show that PRC2 deficiency in adult striatal neurons and in cerebellar Purkinje cells impairs the maintenance of neuron-type specific gene expression. The deficiency in PRC2 has a direct impact on a selected group of genes that is dominated by self-regulating transcription factors normally suppressed in these neurons. The age-dependent progressive transcriptional changes in PRC2-deficient neurons are associated with impaired neuronal function and survival and lead to the development of fatal neurodegenerative disorders in mice. There are 23 total samples. There are three ages, 6 weeks, 3 months and 6 months. There are at least three biological replicates per group. Control samples are age- and sex-matched littermates.

2016-07-29 | E-GEOD-84243 | biostudies-arrayexpress

Microarray analysis of striatal tissue of wild type and Ezh1/Ezh2 dKO mice at 6 weeks, 3 months, and 6 months

Project description:Normal brain function critically depends on the interaction between highly specialized neurons that operate within anatomically and functionally distinct brain regions. The fidelity of neuronal specification is contingent upon the robustness of the transcriptional program that supports the neuron type-specific patterns of gene expression. Changes in neuron type-specific gene expression are commonly associated with neurodegenerative disorders including Huntington’s and Alzheimer’s disease. The neuronal specification is driven by gene expression programs that are established during early stages of neuronal development and remain in place in the adult brain. Here we show that the Polycomb repressive complex 2 (PRC2), which supports neuron specification during early differentiation, contributes to the suppression of the transcription program that can be detrimental for the adult neuron function. We show that PRC2 deficiency in adult striatal neurons and in cerebellar Purkinje cells impairs the maintenance of neuron-type specific gene expression. The deficiency in PRC2 has a direct impact on a selected group of genes that is dominated by self-regulating transcription factors normally suppressed in these neurons. The age-dependent progressive transcriptional changes in PRC2-deficient neurons are associated with impaired neuronal function and survival and lead to the development of fatal neurodegenerative disorders in mice.

2016-07-29 | GSE84243 | GEO

Next-generation sequencing identifies mRNAs targets that experience significant changes in alternative splicing upon PQBP1 knockdown in mouse embryonic cortical neurons

Project description:PQBP1 is a highly conserved protein closely related to neurodegenerative disorders. We identified PQBP1 as an important alternative splicing effector necessary for maintaining normal neuron functions in the brain. In order to explore PQBP1's functions in alternative splicing regulation and neuronal activities, we systematically profiled the alternative splicing targets of PQBP1 in mouse embryonic cortical neurons by RNA-seq. The mRNAs whose alternative splicing are affected by PQBP1 showed tissue-specific functional enrichment especially in neurite outgrowth, with strong Gene Ontology (GO) enrichments for neuron projection development/morphogenesis, dendrite development and axonogenesis. PQBP1's alternative splicing targets are also functionally enriched in RNA splicing, chromatin modification, and ARF signal transduction. We applied RNA-seq to compare the transcriptomes of mock and PQBP1 knockdown mouse embryonic cortical neuron samples.

2013-03-15 | E-GEOD-44402 | biostudies-arrayexpress

Integrative Single-Cell Transcriptomics Reveals Molecular Networks Defining Neuronal Maturation during Neurogenesis

Project description:Neurogenesis in the adult hippocampus contributes to information processing critical for cognition, adaptation, learning and memory, and is implicated in numerous neurological disorders. New neurons are continuously produced from neural stem cells via a well-controlled developmental process. The immature neuron stage defined by doublecortin (DCX) expression is the most sensitive to regulation by extrinsic factors. However, little is known about the dynamic biology within this critical interval that drives maturation and confers susceptibility to regulating signals. This study aims to test the hypothesis that DCX-expressing immature neurons in adult mouse hippocampus progress through developmental stages via activity of specific transcriptional networks. Using single-cell RNA-seq combined with a novel integrative bioinformatics approach, we discovered that individual immature neuron can be classified into distinct developmental subgroups based on characteristic gene expression profiles and subgroup-specific markers. Comparisons between immature and more mature subgroups revealed novel pathways involved in neuronal maturation. Genes enriched in more immature cells shared significant overlap with genes implicated in neurodegenerative diseases, while genes positively associated with neuronal maturation were enriched for autism-related gene sets. Our study thus discovers molecular signatures of individual adult-born immature neurons and unveils potential novel targets for therapeutic approaches to treat neurodevelopmental and neurological diseases. mRNA sequencing and expression estimation in 64 individual DCX-dsRed+ cells isolated from transgenic DCX-dsRed mice by FACS sorting

2016-02-29 | E-GEOD-75901 | biostudies-arrayexpress

Epigenetic regulation of brain region-specific microglia clearance activity

Project description:The rapid elimination of dying neurons and non-functional synapses in the brain is carried out by microglia, the resident myeloid cells of the brain. Here we show that microglia clearance activity in the adult brain is regionally regulated and depends on the rate of neuronal attrition. Cerebellar, but not striatal or cortical, microglia exhibited high levels of basal clearance activity, which correlated with an elevated degree of cerebellar neuronal attrition. Exposing forebrain microglia to apoptotic cells activated gene expression programs supporting clearance activity. We provide evidence that the Polycomb repressive complex 2 (PRC2) epigenetically restricts the expression of genes that support clearance activity in striatal and cortical microglia. Loss of PRC2 led to the aberrant activation of a microglia clearance phenotype, which triggers changes in neuronal morphology and behavior. Our data highlight a key role of epigenetic mechanisms in preventing microglia-induced neuronal alterations that are frequently associated with neurodegenerative and psychiatric diseases.

2018-07-13 | GSE108356 | GEO

Neuronal heterogeneity and stereotyped connectivity in the auditory afferent system

Project description:Spiral ganglion (SG) neurons of the cochlea convey all auditory inputs to the brain, yet the cellular and molecular complexity necessary to decode the various acoustic features in the SG has remained unresolved. Using unbiased single-cell RNA sequencing, we identified four types of SG neurons, including three novel subclasses of type I neurons and the type II neurons, and provide a comprehensive genetic framework that define their potential synaptic communication patterns. The connectivity patterns of the three subclasses of type I neurons with inner hair cells and their electrophysiological profiles suggest that they represent the intensity-coding properties of auditory afferents. Moreover, neuron type specification is already established at birth, indicating a neuronal diversification process independent of neuronal activity. Thus, this work provides a transcriptional catalog of neuron types in the cochlea, which serves as a valuable resource for dissecting cell-type-specific functions of dedicated afferents in auditory perception and in hearing disorders.

2018-09-09 | GSE117055 | GEO

Neural connectivity molecules best identify the heterogeneous clock and dopaminergic cell types in the Drosophila adult brain

Project description:Our recent single-cell sequencing of most adult Drosophila circadian neurons indicated notable and unexpected heterogeneity. To address whether other populations are similar, we sequenced a large subset of adult brain dopaminergic neurons. Their gene expression heterogeneity is similar to that of clock neurons, i.e., both populations have two to three cells per neuron group. There was also unexpected cell-specific expression of neuron communication molecule messenger RNAs: G protein–coupled receptor or cell surface molecule (CSM) transcripts alone can define adult brain dopaminergic and circadian neuron cell type. Moreover, the adult expression of the CSM DIP-beta in a small group of clock neurons is important for sleep. We suggest that the common features of circadian and dopaminergic neurons are general, essential for neuronal identity and connectivity of the adult brain, and that these features underlie the complex behavioral repertoire of Drosophila.

2023-02-25 | GSE198948 | GEO

Next-generation sequencing identifies mRNAs targets that experience significant changes in alternative splicing upon PQBP1 knockdown in mouse embryonic cortical neurons

2013-03-15 | GSE44402 | GEO

Transcription profiling of Drosophila embryonic cell culture and embryonic neural tissues FACS sorted for neuronal type to examine determination the neuronal cellular fate and specific neurotransmitter phenotypes of cells in the nervous system

Project description:We are interested in genes that determine the neuronal cellular fate and specific neurotransmitter phenotypes of cells in the nervous system. The reasons for our interest are two fold. First, identification of the genetic pathways operating in specific types of neurons could explain why they die in neurodegenerative diseases such as Alzheimer?s, Parkinson?s and amyotrophic lateral sclerosis. All of these disorders have in common the property that only certain types of neurotransmitter specific neurons degenerate. Secondly, neuronal cell replacement therapies using differentiated stem cell progeny hold the potential to reverse the devastating consequences of neurodegenerative diseases. The genetic personality of specific kinds of neurons must first be defined in order to use proper cells for neuronal replacement and this information will be essential in directing stem cell differentiation into proper developmental pathways. Our current approach to the problems of specification and neurotransmitter phenotype is to create transgenic animals where different neurotransmitter phenotypes are labeled with a fluorescent reporter gene. Labeled neurons are then isolated using Fluorescence Activated Cell Sorting. The purified populations of neurons are analyzed for their whole genome expression patterns using DNA microarray technology. We have successfully applied this approach using Drosophila cholinergic neurons and are now extending our observations to other classes of neurons that use GABA or glutamate as neurotransmitters. Cholinergic neurons express unique sets of ion channels, receptors and other types of genes. We also see unique sets of transcriptional regulatory proteins, and these may be important in the developmental pathways that result in the production of cholinergic neurons.

2007-07-05 | E-GEOD-1060 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data