Cellular imbalance in proximal and distal lung of CFTR-/- sheep in utero and at birth.

The lung is the major focus of therapeutic approaches for the inherited disorder cystic fibrosis (CF) as without treatment lung disease life-limiting. However, the initiating events that predispose the CF lung to cycles of infection, inflammation and resultant tissue damage are still unclear. Observations of inflammation in the CF lung prior to birth in human and several large animal models suggested an in utero origin for the disease and encouraged a detailed investigation of cell identity prior to birth. Here we used the sheep model of CF (CFTR-/-) and age-matched wild-type sheep to investigate the single cell transcriptomes of proximal and distal lung tissue at 80- and 120 days of gestation and at term (147 days). Single cells from sheep (WT and CF) distal and proximal lung tissue were isolated and analyzed using scRNA-seq.