英国剑桥大学Joo-Hyeon Lee等研究人员合作利用三维人体肺泡干细胞培养模型揭示对SARS-CoV-2的感染反应。2020年10月21日，《细胞—干细胞》杂志在线发表了这项成果。

研究人员利用来源于原发性人类肺组织的人2型肺泡（hAT2）细胞开发了无滋养层的、长期的三维（3D）培养技术，并研究了对SARS-CoV-2的感染反应。通过基于图像的分析和单细胞转录组谱分析，研究人员揭示了受感染hAT2细胞中病毒的快速复制以及干扰素相关基因和促炎基因的表达增加，这表明了强大的内源性先天免疫应答。

进一步追踪传播过程中获得的病毒突变，可从一次病毒进入中有效识别出单个细胞的完全感染。这项研究为SARS-CoV-2的发病机理以及将3D hAT2培养作为呼吸系统疾病模型的应用提供了新见解。

据介绍，SARS-CoV-2是造成当前全球大流行的原因，它感染hAT2细胞。表征发病机理对于开发疫苗和治疗剂至关重要。然而，缺乏反映hAT2细胞的生理学和病理学的模型限制了相关研究。

附：英文原文

Title: Three-dimensional human alveolar stem cell culture models reveal infection response to SARS-CoV-2

Author: 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

Issue&Volume: 2020-10-21

Abstract: Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which is the cause of a present global 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 pro-inflammatory genes in infected hAT2 cells, indicating 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: 10.1016/j.stem.2020.10.004

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30498-7