Cited time in webofscience Cited time in scopus

A longitudinal molecular and cellular lung atlas of lethal SARS-CoV-2 infection in K18-hACE2 transgenic mice

A longitudinal molecular and cellular lung atlas of lethal SARS-CoV-2 infection in K18-hACE2 transgenic mice
Choi, SeunghoonLee, Ju SungKim, SuhyeonLee, Youn WooKim, Gi-CheonHong, Seung-MinAn, Se-HeeNoh, HyunaKim, Kyung EunOn, DainLee, Sang GyuJang, Hui JeongKim, Sung-HeeKim, JiseonSeo, Jung SeonKim, Jeong JinPark, In HoOh, JooyeonKim, Da-JungYoon, Jong-HwiSeok, Sang-HyukLee, Yu JinKim, Seo YeonKim, Young BeenHwang, Ji-YeonLee, Hyo-JungKim, Hong BinPark, Jun WonYun, Jun-WonShin, Jeon-SooSeo, Jun-YoungNam, Ki TaekChoi, Kang-SeukKwon, Ho-KeunLee, Ho-YoungKim, Jong KyoungSeong, Je Kyung
Issued Date
eBioMedicine, v.99
Author Keywords
SARS-CoV-2 infectionK18-hACE2 TG micescRNA-seqLung inflammationTGFβSPP1
Background: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to approximately 500 million cases and 6 million deaths worldwide. Previous investigations into the pathophysiology of SARS-CoV-2 primarily focused on peripheral blood mononuclear cells from patients, lacking detailed mechanistic insights into the virus's impact on inflamed tissue. Existing animal models, such as hamster and ferret, do not faithfully replicate the severe SARS-CoV-2 infection seen in patients, underscoring the need for more relevant animal system-based research. Methods: In this study, we employed single-cell RNA sequencing (scRNA-seq) with lung tissues from K18-hACE2 transgenic (TG) mice during SARS-CoV-2 infection. This approach allowed for a comprehensive examination of the molecular and cellular responses to the virus in lung tissue. Findings: Upon SARS-CoV-2 infection, K18-hACE2 TG mice exhibited severe lung pathologies, including acute pneumonia, alveolar collapse, and immune cell infiltration. Through scRNA-seq, we identified 36 different types of cells dynamically orchestrating SARS-CoV-2-induced pathologies. Notably, SPP1+ macrophages in the myeloid compartment emerged as key drivers of severe lung inflammation and fibrosis in K18-hACE2 TG mice. Dynamic receptor–ligand interactions, involving various cell types such as immunological and bronchial cells, defined an enhanced TGFβ signaling pathway linked to delayed tissue regeneration, severe lung injury, and fibrotic processes. Interpretation: Our study provides a comprehensive understanding of SARS-CoV-2 pathogenesis in lung tissue, surpassing previous limitations in investigating inflamed tissues. The identified SPP1+ macrophages and the dysregulated TGFβ signaling pathway offer potential targets for therapeutic intervention. Insights from this research may contribute to the development of innovative diagnostics and therapies for COVID-19. © 2023 The Author(s) Published by Elsevier B.V.
Files in This Item:


기타 데이터 / 0 B / Adobe PDF download
Appears in Collections:
Department of New Biology Laboratory of Single-Cell Genomics 1. Journal Articles


  • twitter
  • facebook
  • mendeley

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.