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Transciptomic analysis of lungs from mice with selective expression of hACE2 in ATII and club cells after SARS-CoV-2 infection

ABSTRACT: To define the contribution of type II alveolar epithelial cells (ATII) and club cells in SARS-CoV-2-induced lung immunopathology and protective immune responses, we generated mice with selective expression of hACE2 in ATII and club cells, respectively. Our results indicate that SARS-CoV-2 infection elicits a robust immune response dominated by T cell and macrophage activation, primarily driven by infection of ATIIs, with club cells playing a more limited but complementary role.

ORGANISM(S): Mus musculus

PROVIDER: GSE307428 | GEO | 2026/03/03

REPOSITORIES: GEO

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Project description:Purpose: The goals of this study are to compare the difference between WT and hCD147 mice, hACE2 and hCD147 mice lung tissues Transcriptomes after infection with SARS-CoV-2 Methods: After receiving anesthesia with pentobarbital sodium, each mouse of the WT group, hCD147 group, and hACE2 group was infected with SARS-CoV-2 by nasal drip at a dose of 3 x 10^5 TCID50. The lung tissues were take for RNA-seq at 2 dpi. each mouse of the hCD147 group, and hACE2 group was infected with SARS-CoV-2 by nasal drip at a dose of 3 x 10^5 TCID50. The lung tissues were take for RNA-seq at 2 dpi. Results: RNA-seq of lung homogenates from C57BL/6 and hCD147 mice at 2 d.p.i. showed 354 upregulated and 175 downregulated genes). hCD147 mice mediated strong inflammatory responses, including Th17 cell responses, the NF-kappaB pathway and MAPK pathway, etc. The levels of cytokines and chemokines were increased in the lung of hCD147 mice, such as IL6, IL10, ILbeta, CXCL1, CXCL2, CCL2, etc. Analysis of RNA-Seq data of hACE2 mice versus hCD147 mice showed that hACE2 mice had stronger antiviral responses, including type I IFN and IFNalpha/IFNbeta responses, while hCD147 mice showed activation of multiple proinflammatory pathways, which is consistent with clinical features of COVID-19 patients. The significantly upregulated genes during SARS-CoV-2 infection of hACE2 mice enriched in cellular response to IFN-?. The upregulated genes in SARS-CoV-2-infected hCD147 mice were enriched secretory proteins, including ILbeta, IL6 and CXCL1. Conclusions: CD147 mediates potent inflammatory responses in SARS-CoV-2 infection. RNA-seq of lung homogenates from hACE2 and hCD147 mice at 2 d.p.i. showed 354 upregulated and 175 downregulated genes). hCD147 mice mediated strong inflammatory responses, including Th17 cell responses, the NF-kappaB pathway and MAPK pathway, etc. The levels of cytokines and chemokines were increased in the lung of hCD147 mice, such as IL6, IL10, ILbeta, CXCL1, CXCL2, CCL2, etc.

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Transciptomic analysis of lungs from mice with selective expression of hACE2 in ATII and club cells after SARS-CoV-2 infection

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