Emma Rawlins PhD, MRC Senior Non-Clinical 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. A different set of progenitor cells also maintain the slowly turning-over airway epithelium in the adult.
We are studying how the production of different cell types is 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.
Our recent work in the adult mouse tracheal epithelium has uncovered two morphologically identical subpopulations of basal cells: stem cells and long-lived precursors that are already committed to differentiation. And we have shown that active signalling mechanisms are required to maintain quiescence in these cells.
In the mouse embryonic lung we have identified a population of multipotent epithelial progenitors that undergo a steroid-induced change in competence and gene expression during embryogenesis. This switch in progenitor competence underlies the production of airway versus alveolar epithelium and therefore controls the overall capacity of the lung for gas exchange.
We have defined the tissue culture conditions for growing this lung epithelial stem cell population from human embryos as self-renewing organoids. We are now focusing our research on lung conditions related to premature birth using our organoids and analysis of primary human embryonic tissue.
• Laresgoiti U et al. (2016) Lung epithelial tip progenitors integrate Glucocorticoid and STAT3-mediated signals to control progeny fate. Development 143(20): 3686-3699.
• 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.
• 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.