GSE157852

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

Submitted by Sarshan R Pather (University of Pennsylvania, USA) on Sep 11 2020

Platform: ngs – NextSeq 550 (Homo sapiens)

Pubmed: 33010822

Summary 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.

9 Samples

ID	Title	Cell Type	Timepoint	Reported Virus	Virus Species
GSM4776784	Mock 72 hpi rep1	choroid plexus epithelium		Mock	Uninfected
GSM4776785	Mock 72 hpi rep2	choroid plexus epithelium		Mock	Uninfected
GSM4776786	Mock 72 hpi rep3	choroid plexus epithelium		Mock	Uninfected
GSM4776787	SARS-CoV-2 24 hpi rep1	choroid plexus epithelium	24 hrs	SARS-CoV-2	Severe acute respiratory syndrome-related coronavirus
GSM4776788	SARS-CoV-2 24 hpi rep2	choroid plexus epithelium	24 hrs	SARS-CoV-2	Severe acute respiratory syndrome-related coronavirus
GSM4776789	SARS-CoV-2 24 hpi rep3	choroid plexus epithelium	24 hrs	SARS-CoV-2	Severe acute respiratory syndrome-related coronavirus
GSM4776790	SARS-CoV-2 72 hpi rep1	choroid plexus epithelium	72 hrs	SARS-CoV-2	Severe acute respiratory syndrome-related coronavirus
GSM4776791	SARS-CoV-2 72 hpi rep2	choroid plexus epithelium	72 hrs	SARS-CoV-2	Severe acute respiratory syndrome-related coronavirus
GSM4776792	SARS-CoV-2 72 hpi rep3	choroid plexus epithelium	72 hrs	SARS-CoV-2	Severe acute respiratory syndrome-related coronavirus