c-kit(+) cells adopt vascular endothelial but not epithelial cell fates during lung maintenance and repair

Unraveling the fate specification of resident stem cells during lung regeneration is of clinical importance. It has been reported that c-kit(+) progenitor cells resident in the human lung regenerate epithelial lineages upon transplantation into injured mouse lung. Here we test the lineage potential of c-kit(+) cells by inducible genetic lineage tracing. We find that c-kit(+) cells do not contribute to lung epithelium during homeostasis and repair, and instead maintain a vascular endothelial cell fate. These findings call attention to the clinical application of c-kit(+) stem cells as lung epithelial progenitors for the treatment of pulmonary disease.