Tracing the potential of lung progenitors

Abstract

Transplanted lung progenitor cells give rise to specialized epithelial cells, raising new possibilities for treating lung disease.

Figure 1

Schematic of lineage hierarchy and transplantation results. (a) Zuo et al. mark cells using the bovine Krt5-CreER and lsl-LacZ transgenes and initiate lineage tracing before H1N1 infection. β-Gal (purple) imaging shows DASCs as Krt5⁺ (green stripes). DASCs respond to infection by migrating to the interstitial space, proliferating into Krt5⁺ pods and then expressing markers of type 1 (PDPN/1H8) or type 2 (Spc) cells. (b) Vaughan et al. mark cells before H1N1 infection by multiple knock-ins, yet only Krt5-CreER; lsl-tdTomato (red cells) are traced to pods, making up 13% of pod cells. The remaining pod cells (87%) are lineage negative (LNEPs; red border) and Krt5⁻, which respond to infection by migrating to the interstitial space and forming Krt5⁺ pods that potentially will express markers of type 1 (Pdpn) or type 2 (Spc) cells. LNEPs may activate Krt5 expression (green stripes) or give rise to Krt5⁺ cells. (c) Both studies demonstrate a transplantation assay after influenza infection. Zuo et al. use intratracheal instillation of cultured and expanded DASCs, which engraft in the lung and express markers of type 1, type 2 and club cells. Instillation of 10⁶ DASCs is reported to improve the phenotype seen in the Krt6-DTA DASC ablation model. Vaughan et al. use intranasal delivery of freshly isolated LNEPs. Upon engraftment, LNEPs give rise to cells that express Krt5 (green stripes) and markers of type 2 (Spc) or club (CC10) cells.