Airway Basal Cells in Development, Injury-Repair, and Homeostasis

Basal cells (BCs) are multipotent tissue-specific stem cells of a variety of organs including the skin, digestive and respiratory tract. BCs are broadly identified by expression of Krt5, Krt14 and the transcription factor p63. In the adult airways, BCs are not only important for normal maintenance but also crucial for epithelial repair after injury. However, the embryonic origin of these adult stem cells remains elusive. Previous reports showed that p63+ cells appear early during airway development, but these do not express markers of adult BCs, raising the question whether these cells represent BC precursors. Moreover, little was known whether embryonic BCs have an impact in the adult pool of progenitors that mediate responses of the lung to injury or pulmonary diseases. The goal of this thesis is to address these gaps of knowledge using a variety of technologies, including functional and lineage tracing analysis in vivo in mouse genetic models, injury modeling, high-throughput profiling and gene regulation approaches. This thesis is to comprehensively characterize airway BCs in development, injury-repair, and homeostasis. These studies revealed a previously unrecognized broader r