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cell stem cell, 2020.27, 905-919, DOI: https://doi.org/https://doi.org/10.1016/j.stem.2020.10.004
Three-Dimensional Human Alveolar Stem Cell Culture Models Reveal Infection Response to SARSCoV-2
Jeonghwan Youk, Je Hyoung Kim; Kijong Yi; Su Yeon Kim; Kwon Joong Na; Thomas Bleazard; Ho Min Kim; Mick Fellows; Krishnaa T. Mahbubani; Kourosh Saeb-Parsy; Seon Young Kim; Young Tae Kim; Gou Young Koh; Byeong-Sun Choi; Young Seok Ju; Joo-Hyeon Lee
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the cause of a present pandemic, infects human lung alveolar type 2 (hAT2) cells. Characterizing pathogenesis is crucial for developing vaccines and therapeutics. However, the lack of models mirroring the cellular physiology and pathology of hAT2 cells limits the study. Here, we develop a feeder-free, long-term, three-dimensional (3D) culture technique for hAT2 cells derived from primary human lung tissue and investigate infection response to SARSCoV-2. By imaging-based analysis and single-cell tranome profiling, we reveal rapid viral replication and the increased expression of interferon-associated genes and proinflammatory genes in infected hAT2 cells, indicating a 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 defined 3D hAT2 cultures as models for respiratory diseases.
- DOI: https://doi.org/https://doi.org/10.1016/j.stem.2020.10.004
- ISBN or ISSN: 1934-5909
- 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
- This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.