Emma Rawlins PhD, MRC Research Fellow, Member of the Department of Pathology.
Stem and progenitor cells in the mammalian lung
How do stem cells build and maintain the lung? The complicated three-dimensional structure of our lungs is essential for respiration and host defence. Building this structure relies on the correct sequence of division and differentiation events by lung progenitor cells, which also maintain the slowly turning-over airway epithelium in the adult.
How is the production of different cell types controlled in embryonic development and adult maintenance? We apply mouse genetics, live imaging, single-cell molecular analysis and mathematical modelling to understand lung stem cells, with a longer-term aim of directing endogenous lung cells to repair diseased tissue. In the embryonic lung we have identified a population of multipotent epithelial progenitors, which undergo a steroid-induced change in competence and gene expression during embryogenesis
Our recent work in the adult mouse tracheal epithelium uncovered two morphologically identical subpopulations of basal cells: stem cells and long-lived precursors that are already committed to differentiation. We are now exploring how to grow lung epithelial stem cells as self-renewing organoids, and the mechanisms that maintain adult quiescence.
• Balasooriya GI et al. (2016) An FGFR1-SPRY2 Signaling Axis Limits Basal Cell Proliferation in the Steady-State Airway Epithelium. Developmental Cell 37(1):85-97
• Wagstaff L et al. (2016) Mechanical cell competition kills cells via induction of lethal p53 levels. Nat Commun. 7:11373. DOI:10.1038/ncomms11373.
• Watson JK et al. (2015) Clonal Dynamics Reveal Two Distinct Populations of Basal Cells in Slow Turnover Airway Epithelium. Cell Reports 12:1-12
• Rawlins EL (2015) Stem cells: Emergency back-up for lung repair. Nature. 517(7536):556-7.
• Onaitis M et al. (2011) A 10-gene progenitor cell signature predicts poor prognosis in lung adenocarcinoma. Ann Thorac Surg. 91(4):1046-50. [Epub 2011 Feb 25.]
• Rawlins EL et al. (2009) The Id2 distal tip lung epithelium contains individual multipotent embryonic progenitor cells. Development 136:3741-3745
• Rawlins EL et al. (2009) The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium. Cell Stem Cell 4:525-534.