Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Convergent Pathways in Idiopathic Autism Revealed by Time Course Transcriptomic Analysis of Patient-Derived Neurons

ABSTRACT: Purpose: The transcriptional differences between iPSC-derived cortical neurons from patients with idiopathic ASD and unaffected controls was examined over a 135-day course of neuronal differentiation using RNAseq analysis Methods: Induced pluripotent stem cells (5 control iPSC and 6 ASD-specific iPSC) were differentiated into cortical neurons and RNA samples were obtained at two different time points day 35 post differentiation and day 135 post differentiation. RNAseq was performed from the RNA isolated at the different time points and the differentially expressed genes identified. Pathway analysis for gene ontology and biological processes, as well as, weighted gene co-expression network analysis was performed. Results: The results of this analysis show ASD-specific misregulation of genes involved in neuronal differentiation, axon guidance, cell migration, DNA and RNA metabolism, and neural region patterning. Furthermore, functional analysis revealed defects in neuronal migration and electrophysiological activity, providing compelling support for the transcriptome analysis data. Conclusions: Transcriptional analyses of the ASD and control neurons showed ASD-specific molecular phenotypes affecting networks involved in neuronal differentiation, the cytoskeletal matrix structure formation, patterning, DNA and RNA metabolism.

ORGANISM(S): Homo sapiens

PROVIDER: GSE124308 | GEO | 2018/12/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Minimum embedding dimension analysis uncovers reduced network complexity during neuronal differentiation in autism spectrum disorder

Project description:Background: Neuronal activity can be modeled as a nonlinear dynamical system to yield novel measures of neuronal state and dysfunction. We hypothesized that electrical activity during neuronal differentiation would be marked by a reduction in dynamical complexity in autism spectrum disorder (ASD). Methods: Electrical activity of induced pluripotent stem cell (iPSC)-derived neurons from ASD patients and controls were recorded using a multielectrode array (MEA). Minimum embedding dimension (MED) analysis was performed to characterize the complexity present in the electrical recordings of the neuronal cultures during differentiation. Gene expression changes with respect to the MED were analyzed, and gene ontology analysis and the BrainSpan Atlas were used to identify gene enrichments in specific biological pathways, brain regions, and developmental stages. Results: We found that the MED showed a statistically significant deficit in the ASD samples, suggesting that, compared to controls, network complexity is reduced in ASD during neuronal differentiation. MED was correlated to clinical endpoints such as nonverbal intelligence and was associated with 53 differentially expressed genes. These differentially expressed genes were overrepresented in ASD gene lists and pathways related to neurodevelopment, cell morphology, and cell migration. Spatiotemporal analysis also showed a prenatal temporal enrichment in cortical and deep brain structures. Conclusion: Reduced network complexity in ASD was observed by MED analysis during neuronal differentiation, indicating deficits in integrated and synchronized firing. The results present nonlinear dynamical analysis of iPSC-derived neuronal electrical recordings as a new paradigm for the investigation of aberrant brain activity in neurodevelopmental disorders.

2020-05-18 | GSE125020 | GEO

Characterisation of DNA methylomic signatures of induced pluripotent stem cells during neuronal differentiation

Project description:In development, inducing pluripotency and differentiation into different cell types results in global epigenetic changes, although the extent this occurs in induced pluripotent stem cell (iPSC)-based neuronal models has not been extensively characterized. We have differentiated iPSCs (33Qn1 cell line) into cortical neurons and assessed their DNA methylation profile at different time points during differentiation and maturation to identify DNA methylomic trajectories of neuronal aging. Samples were collected at four different time points, these were at the iPSC, neuronal precursor (NPC) and two different terminally differentiated neuronal time points (day 37 and day 58). We have identified loci undergoing significant DNA methylation changes throughout differentiation, have created an epigenetic trajectory signature associated with differentiation/maturation and identified highly connected and influential loci using gene-gene interaction analysis.

2021-06-03 | GSE158089 | GEO

Single cell transcriptomics analysis of induced pluripotent stem cell-derived cortical neurons reveals frequent dual layer identity

Project description:Induced pluripotent stem cell (iPSC)-derived cortical neurons present a powerful new model of neurological disease. Previous work has established that differentiation protocols produce cortical neurons but little has been done to characterise these at cellular resolution. In particular, it is unclear to what extent in vitro two-dimensional, relatively disordered culture conditions recapitulate the development of in vivo cortical layer identity. Single cell multiplex RT-qPCR was used to interrogate the expression of genes previously implicated in cortical layer or phenotypic identity in individual cells. Unexpectedly, 22.7% of neurons analysed frequently co-expressed canonical fetal deep and upper cortical layer markers, and this co-expression was also present at the level of translated protein. By comparing our results to available single cell RNA-seq data from human fetal and adult brain, we observed that this co-expression of layer markers was also seen in primary tissue. These results suggest that establishing neuronal layer identity in iPSC-derived or primary cortical neurons using canonical marker genes transcripts is unlikely to be informative. Single cell RNA-seq of 16 iPSC-derived cortical neurons. This dataset was used for normalization purposes for GSE67835.

2016-01-08 | E-GEOD-69790 | biostudies-arrayexpress

Single cell gene expression profiles for isogenic PTEN panel iPSC-derived cortical organoids

Project description:Alterations in cortical neurogenesis are implicated in neurodevelopmental disorders including autism spectrum disorders (ASDs). Many ASD risk genes have been identified as critical for brain development, but the contribution of genetic backgrounds, although inferred in complex genetic disorders such as ASD, remains unclear. Here, using isogenic induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) and cortical organoid models, we report that a heterozygous PTEN p.I135L mutation found in an ASD patient with macrocephaly dysregulates cortical neurogenesis in an ASD genetic background-dependent fashion. We found that this PTEN p.I135L mutation led to overproduction of NPC subtypes as well as neuronal subtypes including both deep and upper layer neurons in its ASD background, but not when introduced into a control genetic background. ASD and control background differences in neurogenesis, neural development and synapse signaling were also observed. These findings provide experimental evidence that both a PTEN p.I135L mutation and ASD genetic background contribute to cellular features consistent with ASD associated with macrocephaly.

2023-03-20 | GSE214422 | GEO

Bulk RNA-seq on isogenic PTEN panel iPSC-derived neural progenitor cells to study the effect of ASD specific PTEN mutation and the effects of autism genetic background

2023-03-20 | GSE214323 | GEO

Single cell gene expression profiles for iPSC-derived cortical organoids

2023-03-20 | GSE221882 | GEO

Bulk RNA-seq on CTNNB1 mutation CRISPR-corrected ASD iPSC-derived neural progenitor cells as well as one matched control iPSC-derived neural progenitor cells to study the effects of autism genetic background

2023-03-20 | GSE221923 | GEO

Phosphoproteomic analysis of Ank2-mutant mice

Project description:Autism spectrum disorders (ASD) represent neurodevelopmental disorders characterized by social deficits, repetitive behaviors, and various comorbidities, including epilepsy. ANK2, which encodes a neuronal scaffolding protein, is frequently mutated in ASD, but its in vivo functions and disease-related mechanisms are largely unknown. Here, we report that mice with Ank2 knockout restricted to cortical and hippocampal excitatory neurons (Ank2-cKO mice) show ASD-related behavioral abnormalities and juvenile seizure-related death. Ank2-cKO cortical neurons show abnormally increased excitability and firing rate. These changes accompanied decreases in the total level and function of the Kv7.2/KCNQ2 and Kv7.3/KCNQ3 potassium channels and the density of these channels in the enlengthened axon initial segment. Importantly, the Kv7 agonist, retigabine, rescued neuronal excitability, juvenile seizure-related death, and hyperactivity in Ank2-cKO mice. These results suggest that Ank2 regulates neuronal excitability by regulating the length of and Kv7 density in the AIS and that Kv7 channelopathy is involved in Ank2-related brain dysfunctions.

2023-07-20 | PXD041769 | Pride

Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome

Project description:Monogenic neurodevelopmental disorders provide key insights into the pathogenesis of disease and help us understand how specific genes control the development of the human brain. Timothy syndrome is caused by a missense mutation in the L-type calcium channel Cav1.2 that is associated with developmental delay and autism. We generated cortical neuronal precursor cells and neurons from induced pluripotent stem cells derived from individuals with Timothy syndrome. Cells from these individuals have defects in calcium (Ca2+) signaling and activity-dependent gene expression and show abnormalities in differentiation. Neurons from individuals with Timothy syndrome show increased expression of markers of the upper cortical layer and decreased expression of callosal projection markers. In addition, the mutation that causes Timothy syndrome leads to an increase in the production of neurons that synthesize norepinephrine and dopamine. This phenotype can be reversed by treatment with roscovitine, a cyclin-dependent kinase and atypical L-type–channel blocker. These findings provide strong evidence that Cav1.2 regulates the differentiation of cortical neurons in humans and offer new insights into the causes of autism in individuals with Timothy syndrome. Total RNA was isolated from control and TS cells: fibroblasts, iPSCs, neurospheres (at day 7 in suspension), neurons at rest (day 45 of differentiation) and neurons kept in 67mM KCl for 9h. For sample titles, D1,D2 and D3 represent independent differentiation experiments. The number after - represents the iPSC cell line number. GSE25542_non-normalized.txt.gz contains data for 5 outliers.

2011-11-07 | E-GEOD-25542 | biostudies-arrayexpress

Time line RNAseq of iPSC-derived neurons from ASD and control subjects.

Project description:To comprehensively profile early neurodevelopmental alterations in individuals with ASD, we harnessed a time series approach to monitor patient-derived induced pluripotent stem cells (iPSCs) throughout the recapitulation of cortical development. This dataset consists of patient derived neurons that go through all consecutive developmental stages (NSC-derived neurons) as well as a comparative set of iPSC-iNs (neurons generated from the same patients that bypass early NSC-like stages using an Ngn2-transgene approach). For this, we first used fluorescence-activated cell sorting (FACS) to purify a homogeneous population of NSCs based on the expression of the cell-surface markers CD184+/CD271-/CD44-/CD24-/CD15+. To trace ASD and control neurons over time, we performed a series of retroviral lineage-tracing experiments to trace the progenies of dividing NSCs using a retroviral vector expressing a membrane-tagged enhanced green fluorescent protein (eGFP) (CAG::LckN-eGFP). As differentiating neurons express PSA-NCAM on the cell surface, we established a FACS-based protocol for purification of defined subpopulations of retrovirally labeled eGFP+/PSA-NCAM+ double-positive neurons after 2, 4, 7 and 14 days of differentiation. IPSCs were sorted based on the expression of SSEA-4 and TRA1-81 and maturing iPSC-iNs were collected at the indicated days after induction by sorting for eGFP (indicative for the Ngn2 transgene)- and PSA-NCAM-positive cells.

2019-01-07 | E-MTAB-6018 | 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