Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Complete Disruption of Autism-Susceptibility Genes by Gene-Editing Predominantly Reduces Functional Connectivity of Isogenic Human Neurons

ABSTRACT: Complete Disruption of Autism-Susceptibility Genes by Gene-Editing Predominantly Reduces Functional Connectivity of Isogenic Human Neurons

PROVIDER: PRJNA540542 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Complete Disruption of Autism-Susceptibility Genes by Gene-Editing Predominantly Reduces Functional Connectivity of Isogenic Human Neurons

Project description:Complete Disruption of Autism-Susceptibility Genes by Gene-Editing Predominantly Reduces Functional Connectivity of Isogenic Human Neurons

| PRJNA540541 | ENA

Disruption of Autism Spectrum Disorder-Susceptibility Genes Predominantly Reduces Functional Connectivity of Isogenic Human Neurons

Project description:Disruption of Autism Spectrum Disorder-Susceptibility Genes Predominantly Reduces Functional Connectivity of Isogenic Human Neurons

| PRJNA422099 | ENA

Disruption of Autism Spectrum Disorder-Susceptibility Genes Predominantly Reduces Functional Connectivity of Isogenic Human Neurons

Project description:Autism Spectrum Disorder (ASD) is phenotypically and genetically heterogeneous, but genomic analyses have identified candidate susceptibility genes. We present a CRISPR gene editing strategy to insert a protein tag and premature termination sites creating an induced pluripotent stem cell (iPSC) knockout resource for functional studies of 10 ASD-relevant genes (AFF2/FMR2, ANOS1, ASTN2, ATRX, CACNA1C, CHD8, DLGAP2, KCNQ2, SCN2A, TENM1). Neurogenin 2 (NEUROG2)-directed differentiation of iPSCs allowed production of cortical excitatory neurons, and mutant proteins were not detectable. Using both patch-clamp and multi-electrode array approaches, the electrophysiological deficits measured were distinct for different mutations. However, they culminated in a consistent reduction in synaptic activity, including reduced spontaneous excitatory post-synaptic current frequencies in AFF2/FMR2-, ASTN2-, ATRX-, KCNQ2- and SCN2A-null neurons. RNAseq revealed convergence of several neuronal networks. Despite ASD susceptibility genes belonging to different gene ontologies, isogenic stem cell resources can reveal common functional phenotypes, such as reduced functional connectivity.

2018-11-01 | GSE107878 | GEO

Complete Disruption of Autism-Susceptibility Genes by Gene Editing Predominantly Reduces Functional Connectivity of Isogenic Human Neurons.

Project description:Autism spectrum disorder (ASD) is phenotypically and genetically heterogeneous. We present a CRISPR gene editing strategy to insert a protein tag and premature termination sites creating an induced pluripotent stem cell (iPSC) knockout resource for functional studies of ten ASD-relevant genes (AFF2/FMR2, ANOS1, ASTN2, ATRX, CACNA1C, CHD8, DLGAP2, KCNQ2, SCN2A, TENM1). Neurogenin 2 (NGN2)-directed induction of iPSCs allowed production of excitatory neurons, and mutant proteins were not detectable. RNA sequencing revealed convergence of several neuronal networks. Using both patch-clamp and multi-electrode array approaches, the electrophysiological deficits measured were distinct for different mutations. However, they culminated in a consistent reduction in synaptic activity, including reduced spontaneous excitatory postsynaptic current frequencies in AFF2/FMR2-, ASTN2-, ATRX-, KCNQ2-, and SCN2A-null neurons. Despite ASD susceptibility genes belonging to different gene ontologies, isogenic stem cell resources can reveal common functional phenotypes, such as reduced functional connectivity.

| S-EPMC6235011 | biostudies-literature

Enhancers predominantly control transcription initiation

Project description:Enhancers predominantly control transcription initiation

| PRJNA575554 | ENA

A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1

Project description:Tumor microtubes (TMs) connect glioma cells to a network with considerable relevance for tumor progression and therapy resistance. The determination of TM-interconnectivity in individual tumors has been challenging and the impact on patient survival unresolved. Here, a connectivity signature from single-cell RNA-sequenced (scRNA-Seq) xenografted primary glioblastoma (GB) cells has been established using a dye uptake methodology, confirmed with recording of cellular calcium epochs and validated with clinical correlations. Astrocyte-like and mesenchymal-like GB cells have the highest connectivity signature scores in scRNA-sequenced patient-derived xenografts and patient samples. In large GB cohorts, network connectivity correlated with the mesenchymal subtype and dismal patient survival. CHI3L1 has been identified and validated as a robust molecular marker of connectivity with functional relevance. The connectivity signature allows novel insights into brain tumor biology, provides a proof-of-principle that tumor cell TM-connectivity is relevant for patients’ prognosis, and serves as a robust prognostic biomarker.

2023-11-27 | PXD044001 | Pride

SHANK2 mutations associated with autism spectrum disorder cause hyperconnectivity of human neurons

Project description:Heterozygous loss-of-function mutations in the synaptic scaffolding gene SHANK2 are strongly associated with autism spectrum disorder (ASD). To investigate their effect on synaptic connectivity, we generated cortical neurons from induced pluripotent stem cells (iPSC) derived from neurotypic and ASD-affected donors. We developed Sparse coculture for Connectivity (SparCon) assays where SHANK2 and control neurons were differentially labeled and sparsely seeded together on a lawn of unlabeled control neurons. We observed striking increases in total synapse number and dendrite complexity. Dendrite length increases were exacerbated by IGF1 or BDNF treatment. Increased excitatory synapse function in haploinsufficient SHANK2 neurons was phenocopied in gene-edited knockout SHANK2 neurons. Gene correction of an ASD SHANK2 mutation rescued excitatory synapse function supporting a role for SHANK2 as a negative regulator of connectivity in developing human neurons. The transcriptome in these isogenic SHANK2 neurons was deeply perturbed in synaptic and plasticity gene sets and ASD gene modules, and activity dependent dendrite extension was defective. Our unexpected findings provide evidence for hyperconnectivity and profoundly altered transcriptome in SHANK2 neurons derived from ASD subjects.

2019-02-04 | GSE122550 | GEO

Enhancers predominantly control transcription initiation [ATAC-seq]

Project description:Enhancers predominantly control transcription initiation [ATAC-seq]

| PRJNA575557 | ENA

Enhancers predominantly control transcription initiation [RNA-seq]

Project description:Enhancers predominantly control transcription initiation [RNA-seq]

| PRJNA575559 | ENA

Enhancers predominantly control transcription initiation [Capture-C]

Project description:Enhancers predominantly control transcription initiation [Capture-C]

| PRJNA575561 | ENA