Lung Stem Cells -
Defining Molecular Pathways for Self-Renewal and Differentation

Endogenous resident stem/progenitor cells play critical roles in tissue repair after injury and in maintaining the normal homeostatic turn-over of cells in the adult. We have shown that GATA6, which plays a critical role in regulating lung epithelial differentiation, also regulates the temporal appearance and number of distal lung epithelial progenitors called bronchioalveolar stem cells (BASCs). Whether BASCs are a real progenitor cell type in the distal lung has been debated for some time but recent evidence from several labs including ours supports their existence. However, it is unclear what their function is and how they are regulated during development and in the adult after injury. Loss of GATA6 leads to decreased lung epithelial differentiation with the premature appearance of BASCs (these are not apparent until after birth-in a lung epithelial specific loss of GATA6, they are present by E18.5). Moreover, there is a concordant increase in the number of BASCs after lung injury with associated increased mortality due to inefficient regeneration in GATA6 deficient lung epithelium. This increased number of BASCs correlates with an increase in canonical Wnt signaling during development which appears to occur due to dis-regulated non-canonical Wnt signaling. These studies point to the first molecular pathway required for both maintenance of BASC number and the ability to regulate lung regeneration. Future studies are directed towards understanding the molecular pathways regulating the self-renewal and differentiation of BASCs.

• Cardiac Stem Cells and Development
• Wnt Signaling and Lung Development
• Foxp 1/2/4 in Lung and Cardiac Development