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Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium
- Source :
- Cell Stem Cell, bioRxiv
- Publication Year :
- 2020
- Publisher :
- Elsevier Inc., 2020.
-
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. 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 that neurons and astrocytes were sparsely infected, but choroid plexus epithelial cells underwent robust infection. We optimized a protocol to generate choroid plexus organoids from hiPSCs and showed that productive SARS-CoV-2 infection of these organoids is associated with increased cell death and transcriptional dysregulation indicative of an inflammatory response and cellular function deficits. Together, our findings provide evidence for selective SARS-CoV-2 neurotropism and support the use of hiPSC-derived brain organoids as a platform to investigate SARS-CoV-2 infection susceptibility of brain cells, mechanisms of virus-induced brain dysfunction, and treatment strategies.<br />Graphical Abstract<br />HIGHLIGHTS • SARS-CoV-2 minimally infects human neurons and astrocytes in 2D and brain organoids • Model developed for hiPSC-derived choroid plexus organoids (CPOs) • SARS-CoV-2 productively infects CPOs and increases cell death • SARS-CoV-2 CPO infection leads to transcriptional upregulation of inflammatory genes<br />SARS-CoV-2 causes neurological symptoms in a significant portion of patients with COVID-19. Ming and colleagues tested SARS-CoV-2 neurotropism using monolayer neural cells and brain organoids generated from human pluripotent stem cells and show minimal neuron and astrocyte infection, but efficient choroid plexus infection, leading to cell death and functional deficits.
- Subjects :
- Pluripotent Stem Cells
Programmed cell death
Pathology
medicine.medical_specialty
Neurotropism
Biology
Article
brain organoid
03 medical and health sciences
cortical organoid
0302 clinical medicine
Short Article
astrocyte
Neural Stem Cells
Genetics
Organoid
medicine
Choroid Plexus Epithelium
Animals
Humans
Induced pluripotent stem cell
Cells, Cultured
midbrain organoid
030304 developmental biology
Neurons
0303 health sciences
choroid plexus organoid
SARS-CoV-2
hippocampal organoid
Brain
COVID-19
neurotropism
Cell Biology
neuron
Organoids
Viral Tropism
medicine.anatomical_structure
Gene Expression Regulation
Astrocytes
Choroid Plexus
Molecular Medicine
Choroid plexus
Neuron
human iPSCs
030217 neurology & neurosurgery
Astrocyte
hypothalamic organoid
Subjects
Details
- Language :
- English
- ISSN :
- 18759777 and 19345909
- Database :
- OpenAIRE
- Journal :
- Cell Stem Cell
- Accession number :
- edsair.doi.dedup.....b3d6725f236ac40f46e1a85dc1a78d64