Identification of a multipotent lung progenitor for lung regeneration

SummaryWe recently showed that intravenous infusion of mouse or human, fetal or adult lung cells following conditioning of recipient mice leads to lung chimerism within alveolar and bronchiolar lineages, in distinct ‘patches’ containing both epithelial and endothelial cells. We show here, using R26R-Confetti mice as donors, that these multi-lineage patches are derived from a single lung progenitor. FACS of adult mouse lung cells revealed that the putative patch-forming progenitors co-express the endothelial marker CD31 (PECAM-1) and the epithelial marker CD326 (EPCAM). Transplantation of lung cells from transgenic Cre/lox mice expressing membrane GFP under the VEcad promoter (VEcad-Cre-mTmG), led to GFP+ patches comprising both GFP+ endothelial and epithelial cells in vivo, and in ex-vivo culture of CD326+CD31+ progenitors. Single cell mRNAseq of CD326+CD31+ lung cells revealed a subpopulation expressing canonical epithelial and endothelial genes. Such double positive GFP+NKX2.1+SOX17+ cells were also deteceted by immuno-histologial staining in lungs of VEcad-Cre-nTnG (expressing nulear GFP) mice in proximity to blood vessels. These findings provide new insights on lung progenitros and lung development and suggest a potential novel approach for lung regeneration.