tetano
Editor, Senior Moderator
Cell Stem Cell
. 2020 Sep 21;S1934-5909(20)30463-X.
doi: 10.1016/j.stem.2020.09.016. Online ahead of print.
Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium
Fadi Jacob[SUP] 1 [/SUP], Sarshan R Pather[SUP] 2 [/SUP], Wei-Kai Huang[SUP] 3 [/SUP], Feng Zhang[SUP] 4 [/SUP], Samuel Zheng Hao Wong[SUP] 5 [/SUP], Haowen Zhou[SUP] 6 [/SUP], Beatrice Cubitt[SUP] 7 [/SUP], Wenqiang Fan[SUP] 4 [/SUP], Catherine Z Chen[SUP] 8 [/SUP], Miao Xu[SUP] 8 [/SUP], Manisha Pradhan[SUP] 8 [/SUP], Daniel Y Zhang[SUP] 9 [/SUP], Wei Zheng[SUP] 8 [/SUP], Anne G Bang[SUP] 10 [/SUP], Hongjun Song[SUP] 11 [/SUP], Juan Carlos de la Torre[SUP] 12 [/SUP], Guo-Li Ming[SUP] 13 [/SUP]
Affiliations
Abstract
Neurological complications are common in patients with COVID-19. Although severe acute respiratory syndrome coronavirus 2 (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 is 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.
Keywords: COVID-19; SARS-CoV-2; astrocyte; brain organoid; choroid plexus organoid; cortical organoid; hippocampal organoid; human iPSCs; hypothalamic organoid; midbrain organoid; neuron; neurotropism.
. 2020 Sep 21;S1934-5909(20)30463-X.
doi: 10.1016/j.stem.2020.09.016. Online ahead of print.
Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium
Fadi Jacob[SUP] 1 [/SUP], Sarshan R Pather[SUP] 2 [/SUP], Wei-Kai Huang[SUP] 3 [/SUP], Feng Zhang[SUP] 4 [/SUP], Samuel Zheng Hao Wong[SUP] 5 [/SUP], Haowen Zhou[SUP] 6 [/SUP], Beatrice Cubitt[SUP] 7 [/SUP], Wenqiang Fan[SUP] 4 [/SUP], Catherine Z Chen[SUP] 8 [/SUP], Miao Xu[SUP] 8 [/SUP], Manisha Pradhan[SUP] 8 [/SUP], Daniel Y Zhang[SUP] 9 [/SUP], Wei Zheng[SUP] 8 [/SUP], Anne G Bang[SUP] 10 [/SUP], Hongjun Song[SUP] 11 [/SUP], Juan Carlos de la Torre[SUP] 12 [/SUP], Guo-Li Ming[SUP] 13 [/SUP]
Affiliations
- PMID: 33010822
- PMCID: PMC7505550
- DOI: 10.1016/j.stem.2020.09.016
Abstract
Neurological complications are common in patients with COVID-19. Although severe acute respiratory syndrome coronavirus 2 (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 is 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.
Keywords: COVID-19; SARS-CoV-2; astrocyte; brain organoid; choroid plexus organoid; cortical organoid; hippocampal organoid; human iPSCs; hypothalamic organoid; midbrain organoid; neuron; neurotropism.