[논문]Three-Dimensional Human Alveolar Stem Cell Culture Models Reveal Infection Response to SARS-CoV-2

Youk, Jeonghwan; Kim, Taewoo; Evans, Kelly V.; Jeong, Young-Il; Hur, Yongsuk; Hong, Seon Pyo; Kim, Je Hyoung; Yi, Kijong; Kim, Su Yeon; Na, Kwon Joong; Bleazard, Thomas; Kim, Ho Min; Fellows, Mick; Mahbubani, Krishnaa T.; Saeb-Parsy, Kourosh; Kim, Seon Young; Kim, Young Tae; Koh, Gou Young; Choi, Byeong-Sun; Ju, Young Seok; Lee, Joo-Hyeon

doi:10.1016/j.stem.2020.10.004

[해외논문] Three-Dimensional Human Alveolar Stem Cell Culture Models Reveal Infection Response to SARS-CoV-2 원문보기

Cell stem cell, v.27 no.6, 2020년, pp.905 - 919.e10

Youk, Jeonghwan (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology) , Kim, Taewoo (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology) , Evans, Kelly V. (Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge) , Jeong, Young-Il (Division of Viral Disease Research, Center for Infectious Diseases Research, Korea National Institute of Health, Korea Centers for Disease Control and Prevention) , Hur, Yongsuk (BioMedical Research Center, Korea Advanced institute of Science and Technology) , Hong, Seon Pyo (Center for Vascular Research, Institute for Basic Science) , Kim, Je Hyoung (Division of Viral Disease Research, Center for Infectious Diseases Research, Korea National Institute of Health, Korea Centers for Disease Control and Prevention Repu) , Yi, Kijong , Kim, Su Yeon , Na, Kwon Joong , Bleazard, Thomas , Kim, Ho Min , Fellows, Mick , Mahbubani, Krishnaa T. , Saeb-Parsy, Kourosh , Kim, Seon Young , Kim, Young Tae , Koh, Gou Young , Choi, Byeong-Sun , Ju, Young Seok , Lee, Joo-Hyeon

Abstract ▼ AI-Helper

Summary 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. Highlights Long-term 3D culture of primary hAT2 cells in chemically defined conditions SARS-CoV-2 infects in vitro hAT2 models with substantial ultrastructural changes Single-cell RNA-seq finds two cellular states of distinct innate immune phenotypes Mutation analysis reveals single SARS-CoV-2 entry to a hAT2 cell for full infection Graphical Abstract [DISPLAY OMISSION]

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저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

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