An elaborate perspective on club cell regulation

In the murine airway epithelium, basal cells function as stem/progenitor cells that can both self-renew and produce differentiated secretory and ciliated cells. Secretory cells also act as progenitor cells that can both self-renew and produce differentiated club and ciliated cells. Interestingly, these cells are composed of different subpopulations: BASC cells (bronchio-alveolar stem cells), naphthalene-resistant club cells (variant club cells), and non-naphthalene resistant subpopulation. The epithelium of the mature lung differs in cellular composition, function and structural organization along the proximal-distal axis. Based on single-cell sequencing studies of GFP labelled CC10-CreER epithelial cells during mouse lung development and homeostasis, we identified the transcriptional profiles of specific secretory cell populations in mouse lung. The aim of this work is to identify gene markers for secretory cells. Study their molecular mechanism(s), their role in differentiation and proliferation in lung airway epithelial cells. We will confirm in the human system, the newly identified genes by single cell sequencing. Immunofluorescence and real time qPCR will be used to validate in both, ex vivo mouse lung sections and primary human bronchiolar epithelial cells, these new genes. We expect that understanding the cell-differentiation mechanisms in the lung may help us to understand the pathogenesis of devastating lung diseases.