Transcriptomic Signature-Guided Depletion of Intermediate Alveolar Epithelial Cells Ameliorates Pulmonary Fibrosis in Mice
scRNA-seq was used to profile transitional AT2 cells in bleomycin-injured mouse lungs. Using an RNA-sensing strategy, Sprr1a-expressing cells corresponding to Krt8? alveolar differentiation intermediates (ADIs) were selectively labeled and analyzed. scRNA-seq revealed that Sprr1a+ cells display transcriptomic features of transitional epithelial states. These datasets provide a resource to study the role of transitional epithelial populations in lung fibrosis. Overall design: C57BL/6 mice were treated with bleomycin to induce lung fibrosis. At the fibrotic stage, AAV6.2FF vectors encoding Sprr1a sensor RNAs fused to EGFP were delivered to label Sprr1a+ transitional AT2 cells. Labeled (EGFP+) and unlabeled cells were isolated for scRNA-seq using the 10x Genomics Fixed RNA Profiling platform with a custom EGFP probe. Libraries were sequenced on an Illumina NextSeq 2000 and analyzed with Cell Ranger and Scanpy to define Sprr1a+ cell states and compare them with known Krt8+ ADIs.