A bipotential organoid model of respiratory epithelium recapitulates high infectivity of SARS-CoV-2 Omicron variant.
A bipotential organoid model of respiratory epithelium recapitulates high infectivity of SARS-CoV-2 Omicron variant.
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DOI：
10.1038/s41421-022-00422-1
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发表时间：
2022-06-17
期刊：
影响因子：
33.5
通讯作者：
Zhou, Jie
中科院分区：
文献类型：
--
作者：
Chiu, Man Chun;Li, Cun;Liu, Xiaojuan;Yu, Yifei;Huang, Jingjing;Wan, Zhixin;Xiao, Ding;Chu, Hin;Cai, Jian-Piao;Zhou, Biao;Sit, Ko-Yung;Au, Wing-Kuk;Wong, Kenneth Kak-Yuen;Li, Gang;Chan, Jasper Fuk-Woo;To, Kelvin Kai-Wang;Chen, Zhiwei;Jiang, Shibo;Clevers, Hans;Yuen, Kwok Yung;Zhou, Jie
人类呼吸道的气道和肺泡内衬有两种不同类型的上皮细胞，它们是呼吸道病毒的主要靶标。我们先前从肺组织建立了长期扩增的人肺上皮类器官，并开发了一种“近端”分化方案来产生粘膜纤毛气道类器官。然而，具有气道和肺泡分化的双能性的呼吸器官系统仍然难以捉摸。在这里，我们定义了一种“远端”分化方法，从同一来源产生肺泡类器官，用于衍生气道类器官。由I型和II型肺泡上皮细胞（分别为AT 1和AT 2）组成的肺泡类器官在功能上模拟肺泡上皮。维持在肺类器官中的AT 2细胞充当肺泡类器官来源的祖细胞。此外，肺泡类器官维持生产性SARS-CoV-2感染，尽管与气道类器官相比观察到较低的复制适应性。我们进一步优化了二维（2D）气道类器官。在微酸性pH下分化后，2D气道类器官表现出增强的病毒复制，代表了用于模拟SARS-CoV-2高感染性的呼吸道上皮的最佳体外相关性。值得注意的是，Omicron变体比祖先菌株更高的感染性和复制适应性在这些优化的气道类器官中准确地重现。总之，我们已经建立了一个双能类器官培养系统，能够在体外可重复地扩增整个人类呼吸道上皮，用于模拟呼吸道疾病，包括COVID-19。
The airways and alveoli of the human respiratory tract are lined by two distinct types of epithelium, which are the primary targets of respiratory viruses. We previously established long-term expanding human lung epithelial organoids from lung tissues and developed a ‘proximal’ differentiation protocol to generate mucociliary airway organoids. However, a respiratory organoid system with bipotential of the airway and alveolar differentiation remains elusive. Here we defined a ‘distal’ differentiation approach to generate alveolar organoids from the same source for the derivation of airway organoids. The alveolar organoids consisting of type I and type II alveolar epithelial cells (AT1 and AT2, respectively) functionally simulate the alveolar epithelium. AT2 cells maintained in lung organoids serve as progenitor cells from which alveolar organoids derive. Moreover, alveolar organoids sustain a productive SARS-CoV-2 infection, albeit a lower replicative fitness was observed compared to that in airway organoids. We further optimized 2-dimensional (2D) airway organoids. Upon differentiation under a slightly acidic pH, the 2D airway organoids exhibit enhanced viral replication, representing an optimal in vitro correlate of respiratory epithelium for modeling the high infectivity of SARS-CoV-2. Notably, the higher infectivity and replicative fitness of the Omicron variant than an ancestral strain were accurately recapitulated in these optimized airway organoids. In conclusion, we have established a bipotential organoid culture system able to reproducibly expand the entire human respiratory epithelium in vitro for modeling respiratory diseases, including COVID-19.
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影响因子：
64.5
作者：
Hou, Yixuan J.;Okuda, Kenichi;Baric, Ralph S.
通讯作者：
Baric, Ralph S.
影响因子：
64.5
作者：
Kumar PA;Hu Y;Yamamoto Y;Hoe NB;Wei TS;Mu D;Sun Y;Joo LS;Dagher R;Zielonka EM;Wang de Y;Lim B;Chow VT;Crum CP;Xian W;McKeon F
通讯作者：
McKeon F
影响因子：
23.9
作者：
Katsura H;Sontake V;Tata A;Kobayashi Y;Edwards CE;Heaton BE;Konkimalla A;Asakura T;Mikami Y;Fritch EJ;Lee PJ;Heaton NS;Boucher RC;Randell SH;Baric RS;Tata PR
通讯作者：
Tata PR
DOI：
10.1242/dev.163014
发表时间：
2018-05-11
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Chung MI;Bujnis M;Barkauskas CE;Kobayashi Y;Hogan BLM
通讯作者：
Hogan BLM
影响因子：
168.9
作者：
Chan, Jasper Fuk-Woo;Yuan, Shuofeng;Yuen, Kwok-Yung
通讯作者：
Yuen, Kwok-Yung