FIGURE 5.

The transcriptomes of HFLF and hiPSC‐derived EpCAM⁺ cells in FD‐AOs. A, A schematic diagram of scRNA‐seq analysis of FD‐AOs. B, UMAP plots displaying cell clusters in FD‐AOs. Six major types of FD‐EpCAM⁺ cells (FD‐iAT2 cells, mitotic cells, ASCL1⁺ PNECs, INSM1⁺ cells, NKX2‐1⁺ cells, and hepatic‐like cells) and three types of fibroblasts (PDGFRA⁺, WNT5A⁺/PDGFRA⁺, and RARRES1⁺ fibroblasts) were identified. C, Violin plots indicating the gene expression distributions of each fibroblast cluster marker genes. D, Pathway enrichment analysis of PDGFRA⁺, WNT5A⁺/PDGFRA⁺, and RARRES1⁺ fibroblasts. Significantly upregulated genes (P < .05) among PDGFRA⁺, WNT5A⁺/PDGFRA⁺, or RARRES1⁺ fibroblasts compared with either or both of the other cell clusters were used for analysis. The top 100 differential pathways with a P < .05 are shown. E, GSEA using the gene set of β‐catenin degradation by the destruction complex. Significantly up‐ or downregulated genes (P < .05) ranked by the log difference in average gene expression between iAT1 cells and FD‐iAT2 cells were used for analysis. FD‐AOs, fibroblast‐dependent alveolar organoids; GSEA, gene set enrichment analysis; HFLF, human fetal lung fibroblasts; hiPSC, human induced pluripotent stem cell; scRNA‐seq, single‐cell RNA sequencing; UMAP, uniform manifold approximation and projection