biostudies-literaturePeng FNHLBI NIH HHSU.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)1636https://www.ebi.ac.uk/biostudies/studies/S-EPMC12905394biostudies-literatureUnknown17(1)Single-cell RNA sequencing (scRNA-seq) has identified intermediate epithelial states in pulmonary fibrosis, including KRT5-/KRT17+ aberrant basaloid cells in humans and Krt8+ alveolar differentiation intermediates (ADIs) in mice. Their functional contributions to fibrogenesis, however, remain unclear. Here, we introduce an RNA-sensing-dependent protein translation technology that enables selective targeting of Krt8+ ADI cells in vitro and in vivo. Transcriptomic analysis revealed Small Proline-Rich Protein 1 A (SPRR1A) mRNA as a shared marker of murine Krt8+ ADIs and human KRT5-/KRT17+ basaloid cells, distinguishing them from other lung cell populations. Using programmable RNA sensors, we demonstrated selective EGFP-labeling of Krt8+ ADI cells in vivo, which faithfully recapitulated their Nature communicationsTranscriptomic signature-guided depletion of intermediate alveolar epithelial cells ameliorates pulmonary fibrosis in mice.PMC12905394R01 HL156973R01 HL139584HL174994R01 HL174994HL156973HL139584Saito SZheng ZHe CRosas IOAliyari SLasky JAZhou YShan DThannickal VJPeng FSabharwal AYin QJiang CSfalseTranscriptomic signature-guided depletion of intermediate alveolar epithelial cells ameliorates pulmonary fibrosis in mice.Single-cell RNA sequencing (scRNA-seq) has identified intermediate epithelial states in pulmonary fibrosis, including KRT5-/KRT17+ aberrant basaloid cells in humans and Krt8+ alveolar differentiation intermediates (ADIs) in mice. Their functional contributions to fibrogenesis, however, remain unclear. Here, we introduce an RNA-sensing-dependent protein translation technology that enables selective targeting of Krt8+ ADI cells in vitro and in vivo. Transcriptomic analysis revealed Small Proline-Rich Protein 1 A (SPRR1A) mRNA as a shared marker of murine Krt8+ ADIs and human KRT5-/KRT17+ basaloid cells, distinguishing them from other lung cell populations. Using programmable RNA sensors, we demonstrated selective EGFP-labeling of Krt8+ ADI cells in vivo, which faithfully recapitulated their 2026-01-01T00:00:00Z2026 Jan2026-07-15T22:10:17.526Z2026-07-09T10:19:59.896ZS-EPMC129053944151999410.1038/s41467-026-68354-y