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Human iPSC-derived pulmonary epithelial cells infected with SARS-CoV-2 variants in the micro-patterned culture plates [SARS-CoV-2]

ABSTRACT: We infected iPSC-derived pulmonary epithelial cells in the micro-patterned culture plate with the SARS-CoV-2 variants. Analyses of infected alveolar and airway epithelial cells, respectively, revealed the tropism of the variants.

ORGANISM(S): Homo sapiens

PROVIDER: GSE236841 | GEO | 2024/02/29

REPOSITORIES: GEO

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Human iPSC-derived pulmonary epithelial cells infected with SARS-CoV-2 variants in the micro-patterned culture plates [SARS-CoV-2]

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Project description:Ancestral SARS coronavirus-2 (SARS-CoV-2) and variants of concern (VOC) caused a global pandemic with a spectrum of disease variation linked to immune dysfunction. The mechanistic underpinnings of variation related to lung epithelium are relatively understudied. Here, we biobanked lung organoids by preserving stem cell function. We optimized viral infection with H1N1 swine flu and next comprehensively characterized epithelial responses to SARS-CoV-2 infection in phenotypically stable lung organoids from twenty different subjects. We discovered Tetraspanin 8 (TSPAN8) as a novel mediator of SARS-CoV-2-infection. TSPAN8 facilitates SARS-CoV-2 infection rates but does not via enhanced ACE-2-mediated entry. In head-to-head comparisons with Ancestral SARS-CoV-2, Delta- and Omicron- VOC displayed lower overall infection rates of organoids but triggered increased epithelial interferon responses. All variants shared highest tropism for ciliated- and goblet- cells. ACE2- and TSPAN8- expression are universal features of infected cells. TSPAN8-blocking antibodies diminish SARS-CoV-2 infection and may spur novel avenues for COVID-19 therapy.

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