Ontology highlight
ABSTRACT:
PROVIDER: PRJNA759081 | ENA |
REPOSITORIES: ENA
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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:Pluripotent stem cells (PSC) can differentiate inot any cell type of an organism. Their remarkable capability of self-organization enables the formation of three-dimensional structures that resembles miniature organs, including cerebral organoids. These organoids can recreate early steps of the human cerebral cortex development, and show great potential for modeling human diseases, particularly for those with a developmental component. This data evidences stem cell-derived cerebral organoids as a key model to study brain development and neurodevelopmental, neurodegenerative and neuropsychiatric diseases.
2019-11-15 | PXD011605 | Pride
Project description:Chromodomain helicase DNA-binding 8 (CHD8) is one of the most frequently mutated genes causative of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly and hence implicates cortical abnormalities in this form of ASD, the neurodevelopmental impact of human CHD8 haploinsufficiency remains unexplored. Here we combined human cerebral organoids and single cell transcriptomics to define the effect of ASD-linked CHD8 mutations on human cortical development. We found that CHD8 haploinsufficiency causes a major disruption of neurodevelopmental trajectories with an accelerated generation of inhibitory neurons and a delayed production of excitatory neurons alongside the ensuing protraction of the proliferation phase. This imbalance may contribute to the significant enlargement of cerebral organoids in line with the macrocephaly observed in patients with CHD8 mutations. By adopting an isogenic design of patient-specific mutations and mosaic cerebral organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Finally, our results assign different CHD8-dependent molecular defects to particular cell types, pointing to an abnormal and extended program of proliferation and alternative splicing specifically affected in, respectively, the radial glial and immature neuronal compartments. By identifying temporally restricted cell-type specific effects of human CHD8 mutations, our study uncovers developmental alterations as reproducible endophenotypes for neurodevelopmental disease modelling.
2024-01-27 | E-MTAB-11406 | biostudies-arrayexpress
Project description:Amyloid-ß (Aß) plaques are pathological hallmarks of Alzheimer disease. However, the precise neuropathological changes that occur in brain in response to amyloid deposition are largely unknown. To study the molecular mechanism(s) responsible for Aß-mediated neuropathology, we performed a gene expression analysis on frontal neocortical brain tissue of APPPS1 mice compared to their littermate controls.
2014-11-04 | GSE15058 | GEO
Project description:Amyloid-ß (Aß) plaques are pathological hallmarks of Alzheimer disease. However, the precise neuropathological changes that occur in brain in response to amyloid deposition are largely unknown. To study the molecular mechanism(s) responsible for Aß-mediated neuropathology, we performed a gene expression analysis on laser-microdissected brain tissue of Tg2576 mice compared to their littermate controls.
2014-11-04 | GSE15056 | GEO
Project description:Cerebral organoids have emerged as faithful humanoid avatars for modeling numerous advanced neurodevelopmental and pathological processes and additionally serve as a powerful discovery platform for less well-characterized neurobiological programs. Towards this later prospect, we leveraged mass spectrometry-based proteomics to molecularly profile precursor and more committed neural compartments of both human-derived organoids and mid-gestation fetal brain tissue to define overlapping protein-level programs. Interestingly, this included numerous precursor-enriched transcriptional regulatory proteins that were notably not found to be differentially expressed in previous transcriptomic datasets. Specifically, we show that the RuvB-like 2 (RUVBL2) AAA-type ATPase is preferentially expressed in the SOX2-positive compartment of organoids and chemical inactivation leads to precursor cell displacement and apoptosis within the more mature DCX-positive niche. To explore potential clinicopathological correlates of this disruption in organoid cytoarchitecture, we interrogated various clinical datasets, and identified de novo deletions, missense mutations and a novel recurring tandem duplication involving RUVBL2 in patients diagnosed with neurodevelopmental and autism spectrum disorders. Together, our study demonstrates how cell-type specific and phenotype-level profiling of cerebral organoids can help nominate and implicate previously unappreciated genes in neurodevelopment and disease.
2022-04-07 | PXD028911 | Pride
Project description:We generated cerebral organoids from genetically engineered human embryonic stem cells (hESCs), modeling the devastating WOREE syndrome (DEE28), as a prototype for genetic epileptic encephalopathies (EEs). Transcriptome analysis of mutated organoids compared to the WT revealed molecular changes related to both early infantile EEs and specifically to WOREE syndrome.
2021-07-01 | GSE156243 | GEO
Project description:Amyloid-M-CM-^_ (AM-CM-^_) plaques are pathological hallmarks of Alzheimer disease. However, the precise neuropathological changes that occur in brain in response to amyloid deposition are largely unknown. To study the molecular mechanism(s) responsible for AM-CM-^_-mediated neuropathology, we performed a gene expression analysis on laser-microdissected brain tissue of Tg2576 mice compared to their littermate controls. 4 samples; 2 biological replicates of each condition = 2 transgenic versus 2 non-transgenic mice; double amplification of total RNA; only Cy3; no dye-swaps
2014-11-04 | E-GEOD-15056 | biostudies-arrayexpress
Project description:Amyloid-M-CM-^_ (AM-CM-^_) plaques are pathological hallmarks of Alzheimer disease. However, the precise neuropathological changes that occur in brain in response to amyloid deposition are largely unknown. To study the molecular mechanism(s) responsible for AM-CM-^_-mediated neuropathology, we performed a gene expression analysis on frontal neocortical brain tissue of APPPS1 mice compared to their littermate controls. 4 samples; 2 biological replicates of each condition = 2 transgenic versus 2 non-transgenic mice; no amplification of total RNA; Cy3/Cy5 dye-swap design
2014-11-04 | E-GEOD-15058 | biostudies-arrayexpress
Project description:The overall goal of the study was to use in vivo data combined with functional genomics to define gene expression signatures representative of a spectrum of HSV CNS infections. Innate immune deficiencies result in a spectrum of severe clinical outcomes following infection. In particular, there is a strong association between loss of the signal transducer and activator of transcription (Stat) pathway, breach of the blood-brain barrier (BBB), and virus-induced neuropathology. The gene signatures that characterize resistance, disease, and mortality in the virus-infected nervous system have not been defined. Herpes simplex virus type 1 (HSV-1) is commonly associated with encephalitis in humans, and humans and mice lacking Stat1 display increased susceptibility to HSV central nervous system (CNS) infections. In this study, two HSV-1 strains were used, KOS (wild type [WT]), and Δvhs, an avirulent recombinant lacking the virion host shutoff (vhs) function. In addition, two mouse strains were used: strain 129 (control) and a Stat1-deficient (Stat1(-/-)) strain. Using combinations of these virus and mouse strains, we established a model of infection resulting in three different outcomes: viral clearance without neurological disease (Δvhs infection of control mice), neurological disease followed by viral clearance (Δvhs infection of Stat1(-/-) mice and WT infection of control mice), or neurological disease followed by death (WT infection of Stat1(-/-) mice). Through the use of functional genomics on the infected brain stem and liver, we determined gene signatures that were representative of the three infection outcomes. Gender matched, 6- to 8- week old immunocompetent, control 129S6 and 129S6 Stat1 knockout mice were infected corneally with 2x10^6 PFU of either wild type HSV-1, a vhs-null HSV virus, or mock-infected. Brain stems and liver of individual mice were isolated at days 1, 3, 5 and 7 post-inoculation for microarray analysis. For microarray analysis, samples were collected from n=2 animals (1 male, 1 female) per mouse strain and virus strain for each time point. Equal masses of tissue were pooled from two mock-infected mice per time point and run on microarray.
2012-02-21 | E-GEOD-35943 | biostudies-arrayexpress