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ZNF804A transcriptome networks in differentiating human neurons derived from induced pluripotent stem cells

ABSTRACT: The goal of this project is to study transcriptome change by knocking down ZNF804A, a schizophrenia and bipolar disorder candidate gene, in early neurons derived from iPSCs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE54112 | GEO | 2014/07/01

SECONDARY ACCESSION(S): PRJNA235198

REPOSITORIES: GEO

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ZNF804A transcriptome networks in differentiating human neurons derived from induced pluripotent stem cells

Project description:The goal of this project is to study transcriptome change by knocking down ZNF804A, a schizophrenia and bipolar disorder candidate gene, in early neurons derived from iPSCs. Neural progenitor cells (NPCs) were developed from human induced pluripotent stem cells (iPSCs) and transduced by two independent shRNA vectors targeting ZNF804A, a schizophrenia and bipolar disorder candidate gene. After recovery and selection in puromycin, neuronal differentiation was induced. After 14 days, RNA was recovered and analyzed by RNA-seq. The expression profiles were compared with NPCs that were transduced with scrambled control vectors. This corresponds to controls 1-3 and KD 1-3, which was carried out on a male iPSC line. Scramble 1 and 2 and KD1 and 2 are technical replicates. Scrambled 3 and KD 3 were carried out on an independent NPC culture. For control 4 and KD4, neuronal differentiation was induced, and on day 10 the cells were transduced with the same ZNF804A KD and scrambled control vectors used for scrambled control 3 and KD3. In addition, this last set was carried out on a female iPSC line

2014-07-01 | E-GEOD-54112 | biostudies-arrayexpress

Knockdown of the psychosis susceptibility gene ZNF804A alters expression of genes involved in cell adhesion

Project description:Genome-wide association studies have convincingly implicated several novel genes in susceptibility to schizophrenia and bipolar disorder. The first genome-wide significant association with the broad phenotype of psychosis was with a polymorphism in the ZNF804A gene. However, the biological function(s) of ZNF804A have, to date, been entirely unknown. In this study, we manipulated the expression of ZNF804A in neural progenitor cells derived from human cortical neuroepithelium and assessed its effects on the cellular transcriptome. Gene ontology analysis of differentially expressed genes indicated a significant effect of ZNF804A knockdown on the expression of genes involved in cell adhesion, suggesting a role for ZNF804A in processes such as neural migration, neurite outgrowth and synapse formation. Several highly significant gene expression changes were confirmed in repeat cell culture experiments. Most consistent gene expression changes were seen for C2ORF80, a gene of as yet unknown function, and STMN3, a gene involved in neurite outgrowth and axonal and dendritic branching. These data, generated in a hypothesis-free manner, provide a basis for more targeted investigations of ZNF804A function. Total RNA extracted from human neural progenitor cells manipulated with three siRNAs: control siRNA , siRNA_ZNF804A 1 (HSS150612) and siRNA ZNF804A 2 (HSS150613). 4 replicates per group. Genome wide transcript levels were then measured using gene expression microarrays.

2011-11-16 | E-GEOD-28725 | biostudies-arrayexpress

Knockdown of the psychosis susceptibility gene ZNF804A alters expression of genes involved in cell adhesion

2011-11-16 | GSE28725 | GEO

RNA-Seq of human neurons derived from iPS cells Reveals candidate long non-coding RNAs Involved in neurogenesis and neuropsychiatric disorders.

Project description:As a preliminary step towards applying next generation sequencing using neurons derived from patient-specific iPSCs, we have carried out an RNA-Seq analysis on control human neurons. Dramatic changes in the expression of coding genes, long non-coding RNAs (lncRNAs), pseudogenes, and splice isoforms were seen during the transition from pluripotent stem cells to early differentiating neurons. A number of genes that undergo radical changes in expression during this transition include candidates for schizophrenia (SZ), bipolar disorder (BD) and autism spectrum disorders (ASD) that function as transcription factors and chromatin modifiers, such as POU3F2 and ZNF804A, and genes coding for cell adhesion proteins implicated in these conditions including NRXN1 and NLGN1. In addition, a number of novel lncRNAs were found to undergo dramatic changes in expression, one of which is HOTAIRM1, a regulator of several HOXA genes during myelopoiesis. The increase we observed in differentiating neurons suggests a role in neurogenesis as well. Finally, several lncRNAs that map near SNPs associated with SZ in genome wide association studies also increase during neuronal differentiation, suggesting that these novel transcripts may be abnormally regulated in a subgroup of patients. Total RNAs were isolated from both iPS cells and differentiating neurons, and the sequenced material was pre-amplified using the NuGen Ovation amplification system. RNA-Seq libraries were prepared and carried out on Illumina HiSeq200.

2011-10-06 | E-GEOD-32625 | biostudies-arrayexpress

RNA-Seq of human neurons derived from iPS cells Reveals candidate long non-coding RNAs Involved in neurogenesis and neuropsychiatric disorders.

2011-10-06 | GSE32625 | GEO

Schizophrenia risk gene ZNF804A controls ribosome localization and synaptogenesis in developing human neurons

Project description:ZNF804A was amongst the first genes robustly associated with schizophrenia based on findings from large-scale genomic studies. Previous research has implicated ZNF804A inthe regulation of gene expression and synaptic function, but the role this gene plays inneurodevelopment and in relation to schizophrenia pathogenesis remains unclear. To study the function of this gene during neurodevelopment, we generated isogenichuman induced pluripotent stem cells (hiPSCs) with reduced ZNF804A expression, differentiated them into developing cortical glutamatergic neurons and studied theirtranscriptomic, synaptic and protein signatures. Mutant neurons showed modest changes in gene expression. However, high-content confocal imaging revealed increased excitatory synapse density in mutant neurons. Cell-compartment specific proteomic analysis further revealed that mutant neurons had higher levels of ribosomal andtranslational proteins in their neurites, and high-content imaging confirming increased local protein synthesis efficiency. Overall, these results demonstrate that in human developing cortical glutamatergic neurons, ZNF804A regulates excitatory synapse formation potential via increased local protein translation.

2024-01-30 | GSE254523 | GEO

DNA methylation in neurons from post-mortem brains in schizophrenia and bipolar disorder (Methylation)

Project description:We fine-mapped DNA methylation in neuronal nuclei (NeuN+) isolated by flow cytometry from post-mortem frontal cortex of the brain of individuals diagnosed with schizophrenia, bipolar disorder, and controls (n=29, 26, and 28 individuals).

2019-05-03 | GSE112179 | GEO

DNA methylation in neurons from post-mortem brains in schizophrenia and bipolar disorder (Bisulfite-Seq)

2019-05-03 | GSE112524 | GEO

DNA methylation in neurons from post-mortem brains in schizophrenia and bipolar disorder (RNA-Seq)

2019-05-03 | GSE112523 | GEO

Gene expression analysis of neurons differentiated from iPS cells generated from the fibroblasts of monozygotic twins discordant for schizophrenia

Project description:Schizophrenia is heterogenious and polygenic disorder, and thus obtaining geneticly close control samples are valuable to increase the effect size. We obtained skin biopsies from five identical twin pairs discordant for schizophrenia and reprogrammed the cells to induced pluripotent stem cells (iPSCs). They are all Finnish/Caucasians, and the study was approved by ethical commitee in Finland. As schizophrenia affects mostly cognitive functions, we differentiated iPSCs to cortical neurons, moslty excitatory glutamatergic neurons and performed RNA sequencing for transcriptomic changes in neurons from patients with schizophrenia.

2021-05-20 | GSE174704 | GEO

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