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Regenerative Properties of Epithelial Stem Cells in the Proximal Airway
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Regenerative Properties of Epithelial Stem Cells in the Proximal Airway
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Dissertation
Regenerative Properties of Epithelial Stem Cells in the Proximal Airway
2021
Overview
The epithelial cells of the mammalian airways protect the lung from damage and infection. When these airways become damaged following injury or disease, specialized epithelial stem cells (SCs) are activated to regenerate new cells. SC populations reside all along the epithelial layers of the lung. In the proximal airways, basal cells (BCs) of the surface airway epithelium (SAE) serve as the primary SCs of the region. However, other cell types residing within the submucosal glands (SMGs) are also capable of regenerating lost epithelia following injury. The processes that control the proliferation and differentiation of these different SCs in response to injury and disease remain incompletely understood. In this thesis, we discuss the signals and factors that regulate proximal airway epithelial SC function. We provide evidence that the Wnt signaling transcription factor Lef-1 controls BC proliferation and differentiation, and is necessary for proper BC-mediated SAE repair following injury. Furthermore, we demonstrate that SMG-localized SCs can be lineage-traced by their expression of Sox9. In addition, we show that deletion of Sox9 from cultured SMG epithelial SCs reduces clonogenicity and influences lineage fate, suggesting that Sox9 is an important regulator of SMG SC function. Overall, these findings provide novel insights into the function and regulation of airway SCs.
