SRA

Stem cell dynamics in the lung govern homeostasis, repair, and regeneration, yet there is still much unknown about the mechanisms of these processes. Furthermore, incongruencies between murine and human physiology limit the translation of some findings. In this work, we address these limitations by using a transgenic pig model to identify two populations of LGR5+ cells in the lung that are present in the human but that are absent from the mouse. Using RNA sequencing, 3D imaging, organoid models, and differentiation assays, we determine that in the fetal lung, epithelial LGR5 expression is transient in a subpopulation of developing lung bud tips. While epithelial LGR5 expression is absent from postnatal lung, it is reactivated in some organoids derived from basal airway cells. A separate population of LGR5+ cells is mesenchymal, surrounds developing and mature airways, is closely associated with nerve fibers, and acts as a multipotent progenitor cell capable of supporting the airway basal cell niche. These results point to two roles for LGR5 in orchestrating stem and progenitor cell dynamics, and provide a physiologically relevant model for further studies on the role of these populations in repair and regeneration. Overall design: RNA-Seq