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. 2024 Jul 1;56(8):1725–1736. doi: 10.1038/s41588-024-01819-2

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — a, Study design for the mouse BLM lung injury model, analyzing lungs collected at days 7 (d7) and 21 (d21) post oropharyngeal (o.p.) administration (n = 6 for BLM, n = 3 for vehicle per time point (t.p.)), used for Visium experiments. b, DEA of fibrotic regions in human IPF and BLM-treated mice versus controls, with Venn diagrams of DEGs unique and common to human IPF and mouse BLM at d7 or d21 and highlighting genes with inverse expression patterns. c, Integration of Visium and scRNA-seq data (Strunz et al.¹¹; GSE141259) to infer spot cell-type densities, exemplified by inferred AT2 density. d, Averaged cell-type abundance per animal, comparing time points and treatments for selected cell types (Welch two sample t-test, two-sided; n_Vehicle = 3 and n_BLM = 6, per time point). *P < 0.05, **P < 0.01 and ***P < 0.001 (AT2, d7: P = 0.0036; myofibroblast, d7: P = 0.0011, d21: P = 0.0306; Krt8⁺ ADI, d7: P = 0.0042, d21: P = 0.0045; Recr. Mac., d7: P = 0.0006; Res. Mac: d7: P < 0.0001, d21: P < 0.0001). The center line is the median, the box limits are the upper and lower quartiles, the whiskers are 1.5× interquartile range and the points are the value per animal. e, Cell–cell correlation heat maps display cellular colocalization compartments (defined by tree height cutoff, h = 1.5, orange dashed line) across condition and time point. The Sankey diagram illustrates cell type shifts within compartments from vehicle to BLM d7 to BLM d21, with Krt8⁺ ADI (orange line) and myofibroblast (green line) populations highlighted. f, Computed compartment scores (F–H) based on cell-type densities for a BLM d21 lung section. g, Correlation (Pearson) of BLM d21 NMF factor activity and cell-type densities in all spots. The cell-type group colors match their respective compartments (A–H) from prior analysis. h, Comparison between human and mouse d21 NMF analyses using the top 100 factor-driving genes, filtered for factor pairs with a Jaccard index >0.1 to highlight major overlaps. AM, alveolar macrophages; Recr. Mac., recruited macrophages; Res. Mac., resolution macrophages; VECs, vascular endothelial cells; Prolif., proliferating.

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