Fig. 3: Single-cell multiome defines CEBPA-dependent neonatal AT2 cell program and plasticity.

A Sc-multiome UMAPs of purified epithelial cells from Cebpa mutant and littermate control lungs color-coded by cell type (left) and the corresponding percentages (right). Esc, escaper; prolif, proliferating; Tam, 250 μg tamoxifen. See Supplementary Fig. 5A for the sorting strategy. Each sample includes 1 male and 1 female mouse profiled as one sample (same for subsequent sc-multiome experiments). B Dot plot showing the lineage marker (Sun1GFP), Cebpa, and cell type markers. See also feature plots in (C) and Supplementary Fig. 5B. C Sc-multiome UMAP color-coded for genotype (left) and feature plots of metagene scores (top) and representative genes (bottom). The circled population is specific to the mutant, GFP + , and expresses AT1 genes, thus labeled as HOPX + AT1-like cells in (A). See Source Data for metagene lists. D Volcano plot (two-tailed, non-parametric Wilcoxon rank sum test) showing downregulation of AT2 genes and upregulation of progenitor genes in mutant AT2 cells (right) compared to control AT2 cells (left) defined in (A). E Scatter plot correlating changes in the accessibility of scATAC-seq peaks (y-axis) and scRNA-seq expression of their nearest genes (x-axis), color-coded as concordant or discordant as well as the directionality of change. F ScATAC-seq heatmaps and profile plots of decreased and increased peak sets in the mutant and associated log2 fold changes, as well as the corresponding scATAC-seq data in wild type cells and associated Homer motifs. G Feature plots of motif activity scores showing that the mutant has lower CEBP, and higher SOX and TEAD (circle) activities.