Extended Data Figure 7. ATAC-seq reveals distinct differences in open chromatin architecture in AEPs versus AT2s.

(A) ATAC-seq peaks in both AT2 and AEP cells are similar to previously described mouse lung genome wide DNase hypersensitivity profiling. (B) AT2 and AEP ATAC peaks are distributed similarly, predominantly within intergenic regions and introns. (C) GO enrichment analysis of nearest neighbor genes near AT2 vs AEP vs common peaks shows that common peaks are enriched for general cellular housekeeping roles while AT2 open chromatin is enriched near genes associated with exocytosis and cell differentiation. In contrast, AEP peaks are enriched near genes associated with lung development processes. (D–E) Examination of the genes associated with open chromatin in AEPs reveals a strong enrichment for lung endoderm progenitor cell associated transcription factors including members of the Klf, Six, Sox, Nkx2, and Elf/Ets families in AEPs. In contrast, AT2 cell open chromatin is associated with a unique set of transcriptional regulators including members of the NfI and Cebp families which are known to regulate AT2 cell surfactant genes. Detailed methods for ATAC analysis are reported in the Materials and Methods.