RT Journal Article
SR Electronic
T1 Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.28.225151
DO 10.1101/2020.07.28.225151
A1 Fadi Jacob
A1 Sarshan R. Pather
A1 Wei-Kai Huang
A1 Samuel Zheng Hao Wong
A1 Haowen Zhou
A1 Feng Zhang
A1 Beatrice Cubitt
A1 Catherine Z. Chen
A1 Miao Xu
A1 Manisha Pradhan
A1 Daniel Y. Zhang
A1 Wei Zheng
A1 Anne G. Bang
A1 Hongjun Song
A1 Juan Carlos de a Torre
A1 Guo-li Ming
YR 2020
UL http://biorxiv.org/content/early/2020/07/28/2020.07.28.225151.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.