Total RNA sequencing for human induced pluripotent derived cortical neurons
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE164376 | GEO | 2021/01/08
REPOSITORIES: GEO
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Project description:Total RNA sequencing for human induced pluripotent derived cerebral organoids from healthy controls and schizophrenia (SCZ) patients
2019-11-23 | GSE140843 | GEO
Project description:Total RNA sequecing for human induced pluripotent derived cerebral organoids from healthy controls and schizophrenia (SCZ) patients
2020-06-22 | GSE133534 | GEO
Project description:We utilized patient-derived induced pluripotent stem cells (iPSCs) to generate 3D cerebral organoids to model neuropathology of Scz during this critical period. We discovered that Scz organoids exhibited ventricular neuropathology resulting in altered progenitor survival and disrupted neurogenesis. cz organoids principally differed not in their proteomic diversity, but specifically in their total quantity of disease and neurodevelopmental factors at the molecular level. Provides unique insights into the proteome landscape of schizophrenia in patient-derived cerebral organoids
2021-11-17 | PXD027812 | Pride
Project description:To identify morphological and functional phenotypes relevant for SCZ, we generated iPSC-derived dopaminergic neurons from three healthy controls and four patient with schizophrenia. We then performed gene expression profiling analysis using data obtained from RNA-seq of four schizophrenia patients and three controls to determine significantly deregulated genes in schizophrenia dopaminergic neurons.
2024-08-27 | GSE275064 | GEO
Project description:Schizophrenia is a complex and severe neuropsychiatric disorder, with a wide range of debilitating symptoms. Several aspects of its multifactorial complexity are still unknown, and some are accepted to be an early developmental deficiency with a more specifically neurodevelopmental origin. Understanding timepoints of disturbances during neural cell differentiation processes could lead to an insight into the development of the disorder. In this context, human brain organoids and neural cells differentiated from patient-derived induced pluripotent stem cells are of great interest as a model to study the developmental origins of the disease. Here we evaluated the differential expression of proteins of schizophrenia patient-derived neural progenitors, early neurons, and brain organoids. Using bottom-up shotgun proteomics with a label-free approach for quantitative analysis. Multiple dysregulated proteins were found in pathways related to synapses, in line with postmortem tissue studies of schizophrenia patients. However, organoids and immature neurons exhibit impairments in pathways never before found in patient-derived induced pluripotent stem cell studies, such as spliceosomes and amino acid metabolism. In conclusion, here we provide comprehensive, large-scale, protein-level data that may uncover underlying mechanisms of the developmental origins of schizophrenia.
2023-03-11 | PXD026593 | Pride
Project description:Total RNA sequencing for human induced pluripotent derived cortical neurons
| PRJNA690236 | ENA
Project description:Schizophrenia (SCZ) is a psychiatric disorder with a strong genetic determinant. A major hypothesis to explain disease aetiology comprises synaptic dysfunction associated with excitatory-inhibitory imbalance of synaptic transmission, ultimately contributing to impaired network oscillation and cognitive deficits associated with the disease. Here, we studied the morphological and functional properties of a highly defined co-culture of GABAergic and glutamatergic neurons derived from induced pluripotent stem cells (iPSC) from patients with idiopathic SCZ. Our results indicate upregulation of synaptic genes and increased excitatory synapse formation on GABAergic neurons in co-cultures. In parallel, we observed decreased lengths of axon initial segments, concordant with data from postmortem brains from patients with SCZ. Patch-clamp analyses revealed differential processing of excitatory input with markedly increased spontaneous excitatory postsynaptic currents (EPSC) recorded from GABAergic SCZ neurons and decreased spontaneous EPSC from glutamatergic SCZ neurons. Likewise, we observed decreased amplitudes of calcium signals selectively in GABAergic neurons while frequency was increased in both neuronal populations. Finally, MEA recordings from neuronal networks indicate increased synchronization of network activity. In conclusion, our results suggest selective deregulation of neuronal activity and synaptic transmission in SCZ samples, providing evidence for differential signal processing in GABAergic and glutamatergic neurons as a potential base for aberrant network synchronization.
2024-11-25 | GSE282524 | GEO
Project description:Induced pluripotent stem cell (iPSC) technology presents a unique opportunity to model schizophrenia (SCZ) and other neuropsychiatric disorders in vitro by providing investigators with the means to grow patient-specific neurons. Three approaches are possible regarding disease modeling for a genetically heterogenous disorder, like SCZ. One is the draw subjects from the general patient population who have suspected but undefined disease-causing genetic variants. Another is to focus on a common phenotype, such as clinical presentation, response to medications or age of onset. The third is to use patients who have on a common genetic etiology. We have chosen the latter approach and are developing a library of iPSCs from patients with SCZ who harbor chromosome 22q11.2 microdeletions. In this preliminary study involving 4 patients and 4 controls, gene expression profiling was carried out on early differentiating neurons using RNA-seq. Several important observations were made. First, despite the dramatic molecular changes that occur during the reprogramming of a somatic cell into an iPSC, and its subsequent differentiation into neurons, processes that require months of cultivation with multiple changes in growth medium and treatment with a variety of growth factors, we show that 22q11.2 haploinsufficiency at the DNA level is recapitulated in vitro by substantial decreases in the expression of nearly every gene in the deleted region. Overall, transcriptome profiling revealed significant changes in the expression of 604 genes (423 increased in the SCZ samples, 181 decreased; >1.5-fold change, uncorrected p<0.05). Among the differentially expressed genes were a number of SCZ candidates and genes involved in retinoic acid (RA) signaling. In addition, there was some overlap with the differentially expressed genes found in another study using SCZ patients who do not have 22q11.2 del, one of which was CYP26A1, which codes for one of the major enzymes involved in RA metabolism. Although the sample size in this preliminary study is small, the findings support the idea that dysregulated RA-signaling could be a potential target for therapeutic intervention in SZ associated with 22q11.2 del, and perhaps other subgroups of patients. 4 controls and 4 patients
2013-11-01 | E-GEOD-46562 | biostudies-arrayexpress
Project description:From Stertz et al 2021 "Human-induced pluripotent stem cells (hiPSCs) allow for the establishment of brain cellular models of psychiatric disorders that account for a patient’s genetic background. Here, we conducted an RNA-sequencing profiling study of hiPSC-derived cell lines from schizophrenia (SCZ) subjects, most of which are from a multiplex family, from the population isolate of the Central Valley of Costa Rica. hiPSCs, neural precursor cells, and cortical neurons derived from six healthy controls and seven SCZ subjects were generated using standard methodology. Transcriptome from these cells was obtained using Illumina HiSeq 2500, and differential expression analyses were performed using DESeq2 (|fold change|>1.5 and false discovery rate < 0.3), in patients compared to controls. We identified 454 differentially expressed genes in hiPSC-derived neurons, enriched in pathways including phosphoinositide 3-kinase/glycogen synthase kinase 3 (PI3K/GSK3) signaling, with serum-glucocorticoid kinase 1 (SGK1), an inhibitor of glycogen synthase kinase 3β, as part of this pathway. We further found that pharmacological inhibition of downstream effectors of the PI3K/GSK3 pathway, SGK1 and GSK3, induced alterations in levels of neurite markers βIII tubulin and fibroblast growth factor 12, with differential effects in patients compared to controls. While demonstrating the utility of hiPSCs derived from multiplex families to identify significant cell-specific gene network alterations in SCZ, these studies support a role for disruption of PI3K/GSK3 signaling as a risk factor for SCZ." This dataset includes Samples from the manuscript "Convergent genomic and pharmacological evidence of PI3K/GSK3 signaling alterations in neurons from schizophrenia patients" by Stertz et al 2021 published in Neuropsychopharmacology.
2021-08-28 | GSE182875 | GEO
Project description:We established PCCB knockdown human induced pluripotent stem cell (hiPSC) line using CRISPR interference (CRISPRi). The established PCCB knockdown and control hiPSCs were then used to generate human forebrain organoids (hFOs). On day 60 of organoid culture, PCCB knockdown and control hFOs were randomly selected for RNA-sequencing (RNA-seq). We found that differentially expressed genes (DEGs) affected by PCCB knockdown were enriched with GABAergic synapse, synaptic vesicle cycle, neurotransmitter transport, forebrain development, axon development, synaptic organization, and calcium signaling pathways. The DEGs were also significantly overlapped with schizophrenia (SCZ)-associated genes, including genes dysregulated in brains or organoids derived from SCZ patients, and genes reported in SCZ GWAS.
2023-05-02 | GSE226233 | GEO