Lung Lineage Development
During embryonic development, the lung arises from a small group of cells that express the transcription factor Nkx2-1 and form a bud in the foregut endoderm. The lung bud would undergo successive stereotypical branching (branching morphogenesis) and form a complex network of airway conduits and terminally ending in alveolar sacs, where gas exchange with the lung vascular network and the production of surfactants needed for breathing occurs. Lung development begins roughly four weeks post conception and continue up to three years after birth. By the end of development at least 40 different cell types would form this intricate major organ involved in gas exchange, immunity and xeno-metabolism.
Our lab is interested in addressing two fundamentally important questions in lung lineage development:
- How does the lung form from a group of embryonic progenitors and give rise to all the cell types in the human lung?
- How does deregulation of developmental pathways affect the integrity and function of the epithelium in airway diseases such as cystic fibrosis? Specifically, what role does cystic fibrosis transmembrane conductance regulator (CFTR) mutations have on lung lineage development and how does this impact therapies?
To address these questions, we are employing a combination of CRISPR gene-editing tools to generate novel human ES/iPS cell reporters, cellular barcoding, single cell genomics, stem cell organoid cultures and mouse transgenics.