Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium

ABSTRACT: Neurological complications are common in patients with COVID-19. While SARS-CoV-2, the causal pathogen of COVID-19, has been detected in some patient brains, its ability to infect brain cells and impact their function are not well understood, and experimental models using human brain cells are urgently needed. Here we investigated the susceptibility of human induced pluripotent stem cell (hiPSC)-derived monolayer brain cells and region-specific brain organoids to SARS-CoV-2 infection. We found modest numbers of infected neurons and astrocytes, but greater infection of choroid plexus epithelial cells. We optimized a protocol to generate choroid plexus organoids from hiPSCs, which revealed productive SARS-CoV-2 infection that leads to increased cell death and transcriptional dysregulation indicative of an inflammatory response and cellular function deficits. Together, our results provide evidence for SARS-CoV-2 neurotropism and support use of hiPSC-derived brain organoids as a platform to investigate the cellular susceptibility, disease mechanisms, and treatment strategies for SARS-CoV-2 infection.

ORGANISM(S): Homo sapiens

PROVIDER: GSE157852 | GEO | 2020/09/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2

Project description:Why individuals with Down Syndrome (DS, trisomy 21) are particularly susceptible to SARS-CoV-2 induced disease remains largely unclear. The choroid plexus secrets the cerebrospinal fluid and strongly expresses the ACE2 receptor and the chromosome 21 encoded TMPRSS2 protease. To investigate the role of the choroid plexus in SARS-CoV-2 central nervous system infection in DS, we established a new type of brain organoid from DS and isogenic euploid control iPSC that consists of a core of appropriately patterned functional cortical neuronal cell types that is surrounded by a patent and functional choroid plexus (CPCOs). Remarkably, DS-CPCOs not only recapitulated abnormal features of DS cortical development but also revealed defects in ciliogenesis and epithelial cell polarity of the developing choroid plexus. We next demonstrate that the choroid plexus layer facilitates SARS-CoV-2 replication and infection of cortical neuronal cells, and that this is increased in DS-CPCOs. We further show that inhibition of TMPRSS2 activity in DS-CPCOs inhibits SARS-CoV-2 infectivity. We conclude that CPCOs are a useful model for dissecting the role of the choroid plexus in euploid and DS forebrain development and enables screening for therapeutics that can inhibit SARS-CoV-2 induced neuro-pathogenesis.

2023-10-16 | GSE208440 | GEO

Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2

2022-07-26 | GSE208575 | GEO

The landscape of human brain immune response in patients with severe COVID-19

Project description:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has been associated with neurological and neuropsychiatric illness in many individuals. We sought to further our understanding of the relationship between brain tropism, neuro-inflammation and host immune response in acute COVID-19 cases. 3 brain regions (dorsolateral prefrontal cortex, medulla oblongata and choroid plexus) from 5 patients with severe COVID-19 and 4 controls were examined. The presence of virus was assessed by western blot against viral spike protein, as well as viral transcriptome analysis covering >99% of SARS-CoV-2 genome and all potential serotypes. Droplet-based single-nucleus RNA sequencing (snRNA-seq) was performed in the same samples to examine the impact of COVID-19 on transcription in individual cells of the brain. Quantification of viral spike S1 protein and viral transcripts did not detect SARS-CoV-2 in the postmortem brain tissue. However, analysis of 68,557 single-nucleus transcriptomes from three distinct regions of the brain identified an increased proportion of stromal cells, monocytes and macrophages in the choroid plexus of COVID-19 patients. Furthermore, differential gene expression, pseudo-temporal trajectory and gene regulatory network analyses revealed transcriptional changes in cortical microglia associated with a range of biological processes, including cellular activation, mobility and phagocytosis. Despite the absence of detectable SARS-CoV-2 in the brain at time of death, the findings suggest significant and persistent neuroinflammation in patients with acute COVID-19.

2021-06-16 | GSE164485 | GEO

Dysregulation of brain and choroid plexus cell types in severe COVID-19

Project description:Though SARS-CoV-2 primarily targets the respiratory system, patients and survivors can suffer neurological symptoms. Yet, an unbiased understanding of the cellular and molecular processes affected in the brains of COVID-19 patients is still missing. Here, we profile 65,309 single-nucleus transcriptomes from 30 frontal cortex and choroid plexus samples across 14 control (including 1 terminal influenza) and 8 COVID-19 patients. While a systematic analysis yields no molecular traces of SARS-CoV-2 in the brain, we observe broad cellular perturbations which predict that choroid plexus barrier cells sense and relay peripheral inflammation into the brain and show that peripheral T cells infiltrate the parenchyma. We discover COVID-19 disease-associated microglia and astrocyte subpopulations that share features with pathological cell states reported in human neurodegenerative disease. Synaptic signaling of upper-layer excitatory neurons—evolutionarily expanded in humans and linked to cognitive function—are preferentially affected in COVID-19. Across cell types, COVID-19 perturbations overlap with those in chronic brain disorders and reside in genetic variants associated with cognition, schizophrenia, and depression. Our findings and public dataset provide a molecular framework to understand COVID-19 related neurological disease observed now and which may emerge later.

2020-10-22 | GSE159812 | GEO

Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2

Project description:Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2

| PRJNA860166 | ENA

Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2

Project description:Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2

| PRJNA859925 | ENA

SARS-CoV-2 Neurotropism and Single Cell Responses in Brain Organoids Containing Innately Developing Microglia

Project description:Here, we derive human brain organoids with innately developing microglia to investigate the cellular responses to SARS-CoV-2 infection on a single cell level. We find evidence of limited tropism to SARS-CoV-2 for all major cell types and observe extensive neuronal cell death that also include non-infected cells. Single cell transcriptome profiling reveals distinct responses in microglia and astrocytes that share features with cellular states observed in neurodegenerative diseases

2022-12-21 | GSE181422 | GEO

A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection [CUT&RUN]

Project description:COVID-19 is a systemic disease involving multiple organs. Human pluripotent stem cells (hPSCs) derived organoids/cells provide insight into cellular tropism and host response, yet the molecular mechanisms regulating SARS-CoV-2 infection remain poorly defined. Here, we systematically examined changes in transcript profiles caused by SARS-CoV-2 infection at different MOIs for airway organoids (AWOs), alveolar organoids (ALOs) and cardiomyocytes (CMs), and identified several genes, including CIART, that are generally implicated in controlling SARS-CoV-2 infection. AWOs, ALOs, and CMs derived from isogenic CIART-/- hPSCs were significantly resistant to SARS-CoV-2 infection, independent of viral entry. Single-cell RNA-seq further validated the decreased levels of SARS-CoV-2 infection in multi-ciliated cells of AWOs. CUT&RUN, ATAC-seq and RNA-seq analyses found that CIART controls SARS-CoV-2 infection at least in part through regulating NR4A1, a gene also identified from the multi-organoid analysis. Finally, transcriptional profiling and pharmacological inhibition revealed that the Retinoid X Receptor (RXR) pathway regulates SARS-CoV-2 infection downstream of CIART/NR4A1. The multi-organoid platform provides potential therapeutic targets for protection against COVID-19 across organ systems.

2022-12-07 | GSE202966 | GEO

A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection [ATAC-seq]

2022-12-07 | GSE202965 | GEO

A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection [scRNA-seq]

2022-12-07 | GSE202964 | GEO