Fig. 2: A single-cell and single-nucleus atlas of COVID-19 lung.
From: COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets
a, Automatic prediction identifies 28 cell subsets across compartments. UMAP embedding of 106,792 harmonized sc/snRNA-Seq profiles (dots) from 24 tissue samples of 16 lung donors with COVID-19, coloured by automatic annotations (legend). b, Epithelial cell subsets. UMAP embedding of 21,661 epithelial cell or nucleus profiles, coloured by manual annotations, with highly expressed marker genes (boxes). c, d, Cell composition and expression differences between COVID-19 and healthy lung. c, Cell proportions (x axis: mean, bar; 95% confidence intervals, line) in each automatically annotated subset (y axis) in COVID-19 snRNA-Seq (red, n = 16), healthy snRNA-Seq (grey, n = 3) and healthy scRNA-Seq (n = 8, blue). Cell types shown have a COVID-19 versus healthy snRNA-Seq false discovery rate (FDR) of <0.05 (Dirichlet multinomial regression). d, Significance (−log10(P), y axis) versus magnitude (log2(fold change), x axis) of differential expression of each gene (dots; horizontal dashed line, FDR < 0.05) between COVID-19 and healthy lung from a total of 2,000 AT2 cells and 14 studies (two-sided test; Supplementary Methods). e, f, An increased pre-alveolar type 1 transitional cell state (PATS)20,21,22 program in pneumocytes in COVID-19 versus healthy lung. e, Distribution of PATS signature scores (y axis) for 17,655 cells from COVID-19 and 24,000 cells from healthy lung pneumocytes (x axis). P < 2.2 × 10−16 (one-sided Mann–Whitney U test). f, UMAP embedding of 21,661 epithelial cell profiles (dots) coloured by signature level (colour legend, lower right) for the PATS (top) or intrapulmonary basal-like progenitor (IPBLP) cell (bottom) programs. g, Model of epithelial cell regeneration in healthy and COVID-19 lung. In healthy alveoli (top), AT2 cells self-renew (1) and differentiate into AT1 cells (2). In COVID-19 alveoli (bottom), AT2 cell self-renewal (1) and AT1 differentiation (2) are inhibited, resulting in PATS accumulation (3) and recruitment of airway-derived IPBLP cells to alveoli (4).
