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. 2021 Aug 13;10:e66417. doi: 10.7554/eLife.66417

Figure 1. A rationalized approach to building and validating human preclinical models of COVID-19.

A) Whisker plots display relative levels of angiotensin-converting enzyme II (ACE2) expression in various cell types in the normal human lung. The cell types were annotated within a publicly available single-cell sequencing dataset (GSE132914) using genes listed in Table 1. p-values were analyzed by one-way ANOVA and Tukey’s post hoc test. (B) Formalin-fixed paraffin-embedded sections of the human lung from normal and deceased COVID-19 patients were stained for SFTPC, alone or in combination with nucleocapsid protein and analyzed by confocal immunofluorescence. Representative images are shown. Scale bar = 20 µm. (C) Schematic showing key steps generating an adult stem cell-derived, propagable, lung organoid model, complete with proximal and distal airway components for modeling COVID-19-in-a-dish. See Materials and methods for details regarding culture conditions. (D) A transcriptome-based approach is used for cross-validation of in vitro lung models of SARS-CoV-2 infection (left) versus the human disease, COVID-19 (right), looking for a match in gene expression signatures.

Figure 1.

Figure 1—figure supplement 1. Alveolar type II pneumocyte hyperplasia is a pathognomonic feature of lung injury in COVID-19.

Figure 1—figure supplement 1.

(A) Whisker plots display relative levels of TMPRSS2 expression in various cell types in the normal human lung. The cell types were annotated within a publicly available single-cell sequencing dataset (GSE132914) using genes listed in Table 2. p-values were analyzed by one-way ANOVA and Tukey’s post hoc test. (B) Formalin-fixed paraffin-embedded (FFPE) sections of the human lung from deceased COVID-19 patients were analyzed by H&E staining. Representative fields are shown. Images on the right are magnified areas indicated with boxes on the left. Arrows indicate alveolar type II pneumocyte hyperplasia. (C, D) FFPE sections of the human lung from normal and deceased COVID-19 patients were stained for AT2 and club cell markers and either ACE2 or viral nucleocapsid protein and analyzed by confocal immunofluorescence. Representative images are shown. Scale bar = 50 µm. (E) FFPE sections of the human lung from normal and deceased COVID-19 patients were stained for viral nucleocapsid antibody. Representative images are shown. Arrows indicate infected cells.