Secreted Frizzled-Related Protein 1 Controls Distal Lung Formation via Wnt and PDGF Signaling

Bulk RNA sequencing and pathway enrichment analysis detected differentially expressed genes in mesenchymal cells in the saccular stage of development. Ablation of Sfrp1 led to abnormal morphometry in the pseudoglandular, canalicular, saccular, and alveolar stages. Single cell RNA sequencing and proximity ligation in situ hybridization studies confirmed expression of Sfrp1 in mesenchymal cells, predominantly fibroblasts, in early development.

Pathway enrichment analysis revealed changes in signaling pathways within the whole lung and PDGFR + cells in the saccular stage.These findings provide new evidence that Wnts exert their control over sacculation and alveologenesis through fibroblast signaling and differentiation. These results provide an important link between studies demonstrating Wnt signaling patterns in alveologenesis, aberrant Wnt signaling in BPD, and Sfrp1 mediated control of fibroblast differentiation after injury.