美国杜克大学医学院的Purushothama Rao Tata课题组利用基于人类肺干细胞的肺泡球揭示了SARS-CoV-2介导的干扰素应答和肺细胞功能障碍。2020年10月21日,国际知名学术期刊《细胞—干细胞》在线发表了这一成果。
Title: Human lung stem cell-based alveolospheres provide insights into SARS-CoV-2 mediated interferon responses and pneumocyte dysfunction
Author: Hiroaki Katsura, Vishwaraj Sontake, Aleksandra Tata, Yoshihiko Kobayashi, Caitlin E. Edwards, Brook E. Heaton, Arvind Konkimalla, Takanori Asakura, Yu Mikami, Ethan J. Fritch, Patty J. Lee, Nicholas S. Heaton, Richard C. Boucher, Scott H. Randell, Ralph S. Baric, Purushothama Rao Tata
Issue&Volume: 2020-10-21
Abstract: Coronavirus infection causes diffuse alveolar damage leading to acute respiratory distress syndrome. The absence of ex vivo models of human alveolar epithelium is hindering an understanding of COVID-19 pathogenesis. We report a feeder-free, scalable, chemically-defined, and modular alveolosphere culture system for propagation and differentiation of human alveolar type 2 cells/pneumocytes derived from primary lung tissue. Cultured pneumocytes express the SARS-CoV-2 receptor ACE2 and can be infected with virus. Transcriptome and histological analysis of infected alveolospheres mirrors features of COVID-19 lungs, including emergence of interferon mediated inflammatory responses, loss of surfactant proteins, and apoptosis. Treatment of alveolospheres with interferons recapitulates features of virus infection, including cell death. In contrast, alveolospheres pretreated with low dose IFNs show a reduction in viral replication, suggesting the prophylactic effectiveness of IFNs against SARS-CoV-2. Human stem cell-based alveolospheres thus provide novel insights into COVID-19 pathogenesis and can serve as a model for understanding human respiratory diseases.
DOI: 10.1016/j.stem.2020.10.005
Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30499-9
Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:25.269
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx
本期文章:《细胞—干细胞》:Online/在线发表