ZNF804A transcriptome networks in differentiating human neurons derived from induced pluripotent stem cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE54112 | GEO | 2014/07/01
SECONDARY ACCESSION(S): PRJNA235198
REPOSITORIES: GEO
Similar Datasets
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
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
Project description:Large-scale genomic screenings greatly advanced our understanding of the genetic basis of schizophrenia. However, how this translates into neurobiological functioning is not clear. Therefore, we aimed to characterize the function of robust susceptibility gene zinc finger protein 804A (ZNF804A), using a model system of relevant cell type and neurodevelopmental timepoint. Based on previous findings, we hypothesized a role for ZNF804A in local protein translation. CRISPR/Cas9-mediated mutation of the risk gene led to increased synapse formation in human induced pluripotent stem cell (hiPSC)-derived developing glutamatergic forebrain neurons as assessed by high-content confocal imaging. Further, mass spectrometry analysis showed an increased recruitment of ribosomes to mutation neurites. Surface sensing of translation (SUnSET) screening complemented this by demonstrating an increased efficiency of local protein synthesis. Overall, these results introduce a novel cellular function for ZNF804A in a model system relevant to schizophrenia, uncovering some aspects of its neurobiology. Ultimately, findings of this study may aid to identify common mechanisms of susceptibility genes.
2026-03-31 | PXD047788 | Pride
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.
2011-11-16 | GSE28725 | GEO
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
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
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.
2011-10-06 | GSE32625 | GEO
Project description:Sleep disturbances are a common symptom in individuals with schizophrenia and can exacerbate disruptions in cognitive processes like learning and memory. Elucidating pharmacologically targetable molecular pathways perturbed by high-risk schizophrenia genes may improve treatment outcomes. Here, we investigate the relationship between the schizophrenia gene znf804a and sleep and circadian behaviors/pathways. Using multi-day tracking of behavior, we show znf804a mutants display changes in circadian behaviors when external light cues are removed. Using bulk RNA sequencing of fish raised in normal light/dark and dark/dark conditions, we identified altered expression of genes in the core and auxiliary pathways controlling circadian rhythms. Further analysis revealed a znf804a-gene-dosage-dependent reduction in fbxl3a RNA expression. Transcriptomic analysis also revealed shifts in the relative abundance of specific transcripts without changing overall gene expression in genes linked to sleep and circadian pathways, including idh1, suggesting znf804a could influence transcript processing or stability. Together, these findings are the first to link ZNF804A orthologs to sleep and circadian phenotypes in model organisms and identify the regulation of fbxl3a and transcript processing as candidate mechanisms through which this schizophrenia risk gene may influence circadian biology.
2026-07-31 | GSE328219 | GEO
Project description: Not available
| S-EPMC4408091 | biostudies-literature
Project description:We are using induced pluripotent stem cell (iPSC) technology to study neuropsychiatric disorders associated with 22q11.2 microdeletions (del), the most common known schizophrenia (SZ) -associated genetic factor. Several genes in the deleted region have been implicated; one of the more promising candidates is DGCR8, which codes for a protein involved in microRNA (miRNA) biogenesis. We carried out miRNA expression profiling (miRNA-seq) on neurons generated from iPSCs derived from controls and SZ patients with 22q11.2 del. miRNA profiling of 7 SZ samples and 9 Control samples derived from iPSCs
2015-08-01 | E-GEOD-65367 | biostudies-arrayexpress