Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DLG2 knockout reveals neurogenic transcriptional programs underlying neuropsychiatric disorders and cognition

ABSTRACT: DLG2 knockout reveals neurogenic transcriptional programs underlying neuropsychiatric disorders and cognition

PROVIDER: PRJNA722412 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR14252400_1.fastq.gz	Fastqsanger.gz
	SRR14252400_2.fastq.gz	Fastqsanger.gz
	SRR14252401_1.fastq.gz	Fastqsanger.gz
	SRR14252401_2.fastq.gz	Fastqsanger.gz
	SRR14252402_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 72

Similar Datasets

DLG2 knockout reveals neurogenic transcriptional programs underlying neuropsychiatric disorders and cognition

Project description:A complex train of events unfolds during brain development, guided by activation/repression of gene expression programs. It remains unclear how this process is disrupted in disease. Here we integrate human genetics with transcriptomic data from differentiation of human embryonic stem cells into cortical excitatory neurons. This reveals a cascade of transcriptional programs activated during early corticoneurogenesis in vitro and in vivo. Genetic variation in these programs is robustly associated with neuropsychiatric disorders and cognitive function, with variants concentrated in loss-of-function intolerant genes. Neurogenic programs also capture schizophrenia GWAS enrichment previously identified in mature excitatory neurons, suggesting that pathways activated during pre-natal development underlie disease-relevant deficits in mature neuronal function. Down-regulation of these programs in DLG2-/- lines delays expression of cell-type identity and impairs neuronal migration, morphology and action potential generation, validating predicted deficits. These data implicate specific cellular pathways underlying neurodevelopment in the aetiology of multiple neuropsychiatric disorders and cognition.

2021-11-11 | PXD029526 | Pride

DLG2 knockout reveals neurogenic transcriptional programs underlying neuropsychiatric disorders and cognition

Project description:Brain development requires a complex choreography of cell proliferation, specialisation, migration and network formation, guided by the activation and repression of gene expression programs. It remains unclear how this process is disrupted in neuropsychiatric disorders. Here we integrate human genetics with transcriptomic data from the differentiation of human embryonic stem cells into cortical excitatory neurons. This reveals a cascade of transcriptional programs, activated during early corticoneurogenesis in vitro and in vivo, in which genetic variation is robustly associated with neuropsychiatric disorders and cognitive function. Within these early neurogenic programs, genetic risk is concentrated in loss-of-function intolerant (LoFi) genes, capturing virtually all LoFi disease association. Down-regulation of these programs in DLG2 knockout lines delays expression of cell-type identity alongside marked deficits in neuronal migration, morphology and action potential generation, validating computational predictions. These data implicate specific cellular pathways and neurodevelopmental processes in the aetiology of multiple neuropsychiatric disorders and cognition.

2021-10-30 | GSE172199 | GEO

Targeting neural cell senescence reverses neuropsychiatric disorders

Project description:Targeting neural cell senescence reverses neuropsychiatric disorders

| PRJNA635422 | ENA

Transcriptome and chromatin accessibility landscapes across 25 human brain regions expand the susceptibility gene set for neuropsychiatric disorders [RNA-Seq]

Project description:Brain region- and cell-specific transcriptome and epigenome molecular features are associated with heritability for neuropsychiatric traits. Here, we provide an atlas of chromatin accessibility and gene expression in neuronal and non-neuronal cells across 25 distinct regions across cortical and subcortical areas of the human brain from 6 neurotypical controls. We identified extensive gene expression and chromatin accessibility differences across brain regions. We further identified variation in alternative promoter-isoform usage and enhancer-promoter interactions across brain regions and found genes with distinct promoter-isoform usage are strongly enriched for neuropsychiatric risk variants. We identified brain region-specific chromatin co-accessibility and gene-coexpression modules that are robustly associated with genetic risk variants for neuropsychiatric disorders. Using an integrative approach, we identify a novel set of genes that is enriched for neuropsychiatric disorders risk variants but is independent of cell-type specific gene expression and annotated pathways. Our results provide a valuable multi-brain region molecular regulation resource and suggest a unique contribution of epigenetic modifications from the subcortical areas to neuropsychiatric disorders.

2022-08-25 | GSE211792 | GEO

Transcriptome and chromatin accessibility landscapes across 25 human brain regions expand the susceptibility gene set for neuropsychiatric disorders [ATAC-Seq]

2022-08-25 | GSE211822 | GEO

Aberrant intragenic DNA methylation in a neurogenic region in autism spectrum disorders

Project description:Aberrant intragenic DNA methylation in a neurogenic region in autism spectrum disorders

| PRJNA544480 | ENA

A human single cell atlas of the substantia nigra reveals novel cell specific pathways associated with the genetic risk of Parkinson’s disease and neuropsychiatric disorders

Project description:We describe the first human single-nuclei transcriptomic atlas for substantia nigra (SN), generated by sequencing ~ 17,000 nuclei from matched cortical and SN samples. We show that common genetic risk for Parkinson’s disease (PD) is associated with dopaminergic neuron (DaN)-specific gene expression including mitochondrial functioning, protein folding and ubiquitination pathways. We also identified a distinct cell-type association between PD risk and oligodendrocyte-specific expression implicating metabolic and gene expression regulation networks. Beyond PD, we find SN DaNs and GABAergic neurons to be associated with different neuropsychiatric disorders, particularly schizophrenia (SCZ) and bipolar disorder (BP). We identified distinct cortex/SN associations with SCZ genetic risk for both excitatory (synaptic functioning) and dopaminergic neurons (mitochondrial functioning and synaptic signalling). Conditional analyses shows that independent sets of loci associate distinct neuropsychiatric disorders with the same neuronal types. This atlas guides our aetiological understanding by associating SN cell-type expression profiles with specific disease risk.

2020-01-07 | GSE140231 | GEO

Can noninvasive brain stimulation enhance cognition in neuropsychiatric disorders?

Project description:Cognitive impairment is a core symptom of many neuropsychiatric diseases and a key contributor to the patient's quality of life. However, an effective therapeutic strategy has yet to be developed. Noninvasive brain stimulation techniques, namely transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), are promising techniques that are under investigation for a variety of otherwise treatment-resistant neuropsychiatric diseases. Notably, these tools can induce alterations in neural networks subserving cognitive operations and thus may provide a means for cognitive restoration. The purpose of this article is to review the available evidence concerning cognitive enhancing properties of noninvasive brain stimulation in neuropsychiatry. We specifically focus on major depression, Alzheimer's disease, schizophrenia, autism and attention deficit hyperactivity disorder (ADHD), where cognitive dysfunction is a major symptom and some studies have been completed with promising results. We provide a critical assessment of the available research and suggestions to guide future efforts. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

| S-EPMC3725288 | biostudies-literature

The novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders

Project description:The novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders

| PRJNA473671 | ENA

The novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders [ChiRP]

Project description:The novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders [ChiRP]

| PRJNA473677 | ENA