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Human cytomegalovirus dysregulates neurodevelopmental pathways in cerebral organoids

ABSTRACT: Human cytomegalovirus dysregulates neurodevelopmental pathways in cerebral organoids

PROVIDER: PRJNA900793 | ENA |

REPOSITORIES: ENA

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Human cytomegalovirus dysregulates neurodevelopmental pathways in cerebral organoids

Project description:This study investigated the viral mechanisms of fetal neural malformation using in vitro human cerebral organoids to model congenital CMV infection

2024-03-27 | GSE217832 | GEO

Downregulation of Neurodevelopmental Gene Expression in iPSC-Derived Cerebral Organoids Upon Infection by Human Cytomegalovirus

Project description:Downregulation of Neurodevelopmental Gene Expression in iPSC-Derived Cerebral Organoids Upon Infection by Human Cytomegalovirus

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Cerebral organoids proteomics - Human Cerebral Organoids and Fetal Brain Tissue Share Proteomic Similarities

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2019-11-15 | PXD011605 | Pride

Downregulation of Neurodevelopmental Gene Expression in iPSC-Derived Cerebral Organoids Upon Infection by Human Cytomegalovirus

Project description:We report the application of bulk RNA sequencing on cerebral organoids infected with HCMV TB40eGFP virus or uninfected, within the infected groups the organoids were sorted into 3 distinct populations prior to sequencing based on GFP expression as a proxy for level of infection. These populations have been denoted GFP (+), GFP Inter, GFP (-), for each sorted population 3 organoids of the same line and from the same differentiation were combined to ensure sufficient cell numbers for bulk sequencing analysis.

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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

Conserved proteomic programs between human cerebral tissue and organoids implicate RUVBL2 in neurodevelopment and disease

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.

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Single-cell ATAC-seq of bonobo cerebral organoids

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2019-10-16 | E-MTAB-8089 | biostudies-arrayexpress

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Project description:Bulk ATAC-seq was performed on human, chimpanzee, bonobo, and macaque stem cell-derived cerebral organoids. ATAC-seq was performed on day 60 (2 months old) and day 120 (4 months old) cerebral organoids.

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