Cellular and molecular characterization of the mesenchymal niche for bronchiolar epithelial progenitor cells after naphthalene injury in mice

Objective:

We have previously shown that ASMCs constitute a mesenchymal niche for bronchiolar epithelial progenitor cells after naphthalene (NA) injury (Volckaert et al., 2011). Recent work by Peng et al. (2015), showed that Gli1-positive cells around the airway could also contribute to this niche. Using lineage tracing-based approach combined with gain/loss of function for Ctnnb1 and Fgf10 expression, we aim to better characterize the mesenchymal niche at the cellular and molecular level.

Results:

Deletion of Ctnnb1 using the Acta2-CreERT2 transgenic line before and after NA injury delays epithelial regeneration while deletion only before injury does not impact epithelial repair. Expression of a stable form of Ctnnb1 in Acta2-positive cells after injury enhanced epithelial repair. Deletion of Fgf10 before and after NA injury also delayed epithelial regeneration. Deletion of Fgf10 before NA injury also lead to decreased epithelial repair and was associated with Wnt7b downregulation. Lineage tracing of Fgf10-positive cells (Fgf10CreERT2/+; Tomatoflox/+) labeled before NA injury shows accumulation of RFP-positive Acta2-negative cells around the bronchi at day 3.

Conclusions:

Our results establish a new paradigm for further experiments addressing the function of signaling pathways in the different components of the mesenchymal niche for bronchiolar epithelial progenitor cells.