Contribution of astrocytes to familial risk and clinical manifestation of Schizophrenia
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA790749 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17276302.fastq.gz | Fastqsanger.gz | |||
| SRR17276303.fastq.gz | Fastqsanger.gz | |||
| SRR17276304.fastq.gz | Fastqsanger.gz | |||
| SRR17276305.fastq.gz | Fastqsanger.gz | |||
| SRR17276306.fastq.gz | Fastqsanger.gz |
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Project description:This SuperSeries is composed of the SubSeries listed below.
2021-12-20 | GSE191250 | GEO
Project description:Previous studies have implicated several brain cell types in schizophrenia (SCZ), but the genetic impact of astrocytes is unknown. Considering their high complexity in humans, astrocytes are likely key determinants of neurodevelopmental diseases, such as SCZ. Human induced pluripotent stem cell (hiPSC)-derived astrocytes differentiated from five monozygotic twin pairs discordant for SCZ and five healthy subjects were studied for alterations related to high genetic risk and clinical manifestation of SCZ in astrocyte transcriptomics, neuron-astrocyte co-cultures, and in humanized mice. We found gene expression and signaling pathway alterations related to synaptic dysfunction, inflammation, and extracellular matrix components in SCZ astrocytes, and demyelination in SCZ astrocyte transplanted mice. While Ingenuity Pathway Analysis identified SCZ disease and synaptic transmission pathway changes in SCZ astrocytes, the most consistent findings were related to collagen and cell adhesion associated pathways. Neuronal responses to glutamate and GABA differed between astrocytes from control persons, affected twins, and their unaffected co-twins and were normalized by clozapine treatment. SCZ astrocyte cell transplantation to the mouse forebrain caused gene expression changes in synaptic dysfunction and inflammation pathways of mouse brain cells and resulted in behavioral changes in cognitive and olfactory functions. Differentially expressed transcriptomes and signaling pathways related to synaptic functions, inflammation, and especially collagen and glycoprotein 6 pathways indicate abnormal extracellular matrix composition in the brain as one of the key characteristics in the etiology of SCZ.
| S-EPMC9306586 | biostudies-literature
Project description:Previous studies have implicated several brain cell types in schizophrenia, but the genetic impact of astrocytes is unknown. Considering their high complexity in humans, astrocytes are likely key determinants of neurodevelopmental diseases. Human induced pluripotent stem cell (hiPSC) -derived astrocytes differentiated from five monozygotic twin pairs discordant for schizophrenia and five healthy subjects were studied for alterations related to high genetic risk and clinical manifestation of SCZ in astrocyte transcriptomics.
2021-12-20 | GSE191248 | 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. ??Molecular and functional abnormalities in astrocytes play a role in the etiology and pathogenesis of schizophrenia. In this study, human induced pluripotent stem cells (hiPSC)-derived astrocytes from schizophrenia patients were investigated regarding their proteome, inflammatory responses, and their secretome effect on vascularization. Proteomic analysis revealed alterations in proteins related to immune function and vascularization. Taken together, our results suggest that schizophrenia astrocytes are immunologically dysfunctional which might affect vascularization through secreted factors.
2023-04-27 | PXD031640 | Pride
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. ??Molecular and functional abnormalities in astrocytes play a role in the etiology and pathogenesis of schizophrenia. In this study, human induced pluripotent stem cells (hiPSC)-derived astrocytes from schizophrenia patients were investigated regarding their proteome, inflammatory responses, and their secretome effect on vascularization. Proteomic analysis revealed alterations in proteins related to immune function and vascularization. Taken together, our results suggest that schizophrenia astrocytes are immunologically dysfunctional which might affect vascularization through secreted factors.
2023-04-27 | PXD031650 | Pride
Project description:Contribution of differential cell-specific methylation to schizophrenia
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Project description:Contribution of differential cell-specific methylation to schizophrenia [RNA-seq]
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Project description:To address the heterogeneity of gene regulation and expression in cell types of a brain region with strong evidence for relevance to schizophrenia, we carried out whole genome methylation and expression analyses using post-mortem brain tissue from BA46 that underwent fluorescence-activated nuclei sorting (FANS). Importantly, we used whole genome bisulfite sequencing (WGBS) for methylation quantification to have an unbiased assessment of epigenetic modifications associated with schizophrenia, and additionally carried out whole genome sequencing (WGS) of the brain samples to account for genetic background differences. We found that a number of schizophrenia GWAS loci overlap with sites of cell-specific differential methylation in schizophrenia brain tissue. Differential methylation is also associated with differential gene expression in a cell-specific manner. Co-expression network analysis can identify groups of genes that are enriched for differentially methylated regions in each cell type, and these groups of co-expressed genes underscore shared molecular pathways that might be at risk in schizophrenia. Together, these data indicate that the integration of multiple levels of data in a cell-specific manner can provide novel biological insights into complex genetic disorders such as schizophrenia.
2019-06-25 | GSE107638 | GEO
Project description:The objective is to quantify the contribution of genetic and common environmental effects in the familial resemblances of whole blood genome-wide gene expression levels. We also make comparisons with familial resemblances in blood leukocytes genome-wide DNA methylation levels in the same cohort in order to further investigate biological mechanims.
2018-05-18 | GSE114620 | GEO
Project description:Genetic studies have suggested a role for glial pathology in the genesis of schizophrenia (SCZ). To assess the nature of SCZ-associated human glial dysfunction in vivo, we established human glial chimeric mice using glial progenitor cells (GPCs) produced from induced pluripotential cells (hiPSCs), derived from patients with juvenile-onset schizophrenia or healthy controls. To this end, hiPSC GPCs were implanted neonatally into either immunodeficient myelin wild-type mice, in which donor GPCs remained as progenitors or became astrocytes, or into myelin-deficient shiverer mice, in which the GPCs also gave rise to oligodendrocytes. When implanted into shiverers, the SCZ-derived GPCs exhibited less expansion in the white matter than did control GPCs, instead migrating prematurely into the cortex. The SCZ GPC-transplanted shiverers were consequently hypomyelinated relative to control GPC-engrafted mice. When established instead in myelin wild-type hosts, the SCZ hiPSC glial chimeras manifested markedly delayed and diminished astrocytic differentiation, which was associated with diminished prepulse inhibition and an aberrant behavioral phenotype across multiple modalities. Accordingly, RNA-seq revealed significant differences in both glial differentiation-associated and synaptic gene expression by SCZ GPCs. These data suggest a potent contribution of cell-autonomous glial dysfunction to the development of schizophrenia, and provide a model for the in vivo assessment of human glial pathology in this disorder.
2017-07-20 | GSE86906 | GEO