Identifying GFAP-expressing cell susceptibility to SARS-CoV-2 infection using human iPSC-derived neural cells

Neurological manifestations are common in COVID-19. However, a key limitation to understanding the mechanisms and developing new therapeutic approaches is the lack of a suitable testing model. In this study, we developed 2D iPSC-derived neural cells to investigate the mechanism underlying the neurotropism of SARS-CoV-2. After two weeks of differentiation, these cells exhibited several cortical brain cell subtypes, as determined by the transcription levels of key marker genes. Interestingly, this heterogeneity of cellular subtypes is comparable to 10-month-old brain organoids developed in an earlier study. Our 2D neural model was predominantly susceptible to SARS-CoV-2 infection in the astrocyte subpopulation. The expression of SARS-CoV-2 entry factors in the astrocyte subpopulation was further explored. Notably, the cells with high expression of BSG were predominately found in the astrocytes. Taken together, our findings demonstrate the benefits of our 2D iPSC-derived neural cell model in elucidating the neurotropism of SARS-CoV-2 and its underlying mechanisms. This model may also be useful for studying the neurotropism of other viruses.