Walking along the Fibroblast Growth Factor 10 Route: A Key Pathway to Understand the Control and Regulation of Epithelial and Mesenchymal Cell-Lineage Formation during Lung Development and Repair after Injury

Figure 4

Epithelial stem-cell tree during lung development. The initial multipotent progenitor cells (Id2⁺, Sox9⁺), present throughout the lung epithelium up to E13.5, give rise to bronchiolar (proximal) and alveolar (distal) progenitors. As development proceeds, subsequent lineages are formed from these proximal (Sox2⁺) or distal (Id2⁺, Sox9⁺) epithelial progenitors. Most of the resulting cell types (such as p63⁺ basal cells, neuroendocrine cells, AECI, AECII, ciliated cells, and goblet cells) are unipotent. Clara cell progenitors (variant Clara cells) are at least bipotent as they can give rise to the secretory and ciliated lineages. These cells can be distinguished from mature Clara cells by the lack of cytochrome P450 expression. We also propose that the 6β4-double positive cells and the BASCs (Scgb1a1⁺, Sftpc⁺) are formed during lung development. The origin of these cells is still unclear (orange dashed lines). Their respective contribution to the proximal or distal epithelial lineages during normal development is likely minimal (blue dashed lines). BASC: bronchoalveolar stem cell.