RT Journal Article
SR Electronic
T1 Robust three-dimensional expansion of human adult alveolar stem cells and SARS-CoV-2 infection
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.10.194498
DO 10.1101/2020.07.10.194498
A1 Jeonghwan Youk
A1 Taewoo Kim
A1 Kelly V. Evans
A1 Young-Il Jeong
A1 Yongsuk Hur
A1 Seon Pyo Hong
A1 Je Hyoung Kim
A1 Kijong Yi
A1 Su Yeon Kim
A1 Kwon Joong Na
A1 Thomas Bleazard
A1 Ho Min Kim
A1 Natasha Ivory
A1 Krishnaa T. Mahbubani
A1 Kourosh Saeb-Parsy
A1 Young Tae Kim
A1 Gou Young Koh
A1 Byeong-Sun Choi
A1 Young Seok Ju
A1 Joo-Hyeon Lee
YR 2020
UL http://biorxiv.org/content/early/2020/07/10/2020.07.10.194498.abstract
AB Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which is the cause of a present global pandemic, infects human lung alveolar cells (hACs). Characterising the pathogenesis is crucial for developing vaccines and therapeutics. However, the lack of models mirroring the cellular physiology and pathology of hACs limits the study. Here, we develop a feeder-free, long-term three-dimensional (3D) culture technique for human alveolar type 2 (hAT2) cells, and investigate infection response to SARS-CoV-2. By imaging-based analysis and single-cell transcriptome profiling, we reveal rapid viral replication and the increased expression of interferon-associated genes and pro-inflammatory genes in infected hAT2 cells, indicating robust endogenous innate immune response. Further tracing of viral mutations acquired during transmission identifies full infection of individual cells effectively from a single viral entry. Our study provides deep insights into the pathogenesis of SARS-CoV-2, and the application of long-term 3D hAT2 cultures as models for respiratory diseases.Competing Interest StatementThe authors have declared no competing interest.