DDT promotes growth of alveolar organoids from lung tissue of COPD patients.
(a) Quantification of the total number of human organoids (alveolar and mixed) and their size on day 14 following treatment with and without rhDDT (100 ng/ml). Lung tissue was obtained from eight patients with COPD GOLD stage I-IV. Groups in panel a were compared using a paired t test, p<0.05 was considered significant. (b) Upper panels: light microscopy images of human alveolar and mixed organoid morphologies; lower panels: immunofluorescence images of human alveolar and mixed organoids stained for acetylated tubulin (ACT, red), pro-surfactant protein C (SFTPC, green), and DAPI (blue). (c) Quantification of the total number of organoids (alveolar and mixed) on day 14 following treatment with and without rhDDT (100 ng/ml) or/and the ACKR3-blocking nanobody VUN702 (1 μM). Lung tissue was obtained from five patients with COPD GOLD stage I-IV. Each color designates one patient. Groups in panel a were compared using a Friedman test with Dunn's correction for multiple testing, p<0•05 was considered significant. Groups in panel c were compared using a two-way ANOVA, p<0•05 was considered significant. (d) Upper panel: UMAPs of DDT gene expression in different types of epithelial cells from lung tissue of patients with COPD or control donors. UMAPs are color labelled by cell type (upper left), DDT expression (upper middle), and disease status (upper right). Lower panel: Comparison of DDT gene expression in different types of lung epithelial cells from lung tissue of patients with COPD or control donors. Data taken from the COPDcellatlas.com. ATI= alveolar type I cells; ATII= alveolar type II cells; PNEC= pulmonary neuroendocrine cells. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)