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Hong, Seon Pyo
혈관 연구단
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Three-Dimensional Human Alveolar Stem Cell Culture Models Reveal Infection Response to SARS-CoV-2

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Title
Three-Dimensional Human Alveolar Stem Cell Culture Models Reveal Infection Response to SARS-CoV-2
Author(s)
Jeonghwan Youk; Taewoo Kim; Kelly V. Evans; Young-Il Jeong; Yongsuk Hur; Seon Pyo Hong; 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
Subject
3D cultures, ; alveolar stem cells, ; COVID-19, ; electron microscopy, ; human alveolar type 2 cells, ; infection, ; interferon, ; interferon-stimulating genes, ; SARS-CoV-2, ; single-cell RNA-seq
Publication Date
2020-12-03
Journal
CELL STEM CELL, v.27, no.6, pp.905 - +
Publisher
CELL PRESS
Abstract
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 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 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.
URI
https://pr.ibs.re.kr/handle/8788114/7513
DOI
10.1016/j.stem.2020.10.004
ISSN
1934-5909
Appears in Collections:
Center for Vascular Research(혈관 연구단) > 1. Journal Papers (저널논문)
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