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Emma Rawlins

rawlinsEmma Rawlins PhD, MRC Research Fellow, Member of the Department of Pathology.

Europe PMC | Pubmed

 

 

 

 

Stem and progenitor cells in the mammalian lung

2016 RawlinsHow 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.

Selected publications:

• 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.

groupRawlins2015

Plain English

Our ability to breathe at birth requires that during embryonic development our lungs make many types of specialised cells, arranged in a specific structure. This structure must then be maintained throughout life, even when the air that we breathe is contaminated by pollutants and toxins.

Building and maintaining the lung involves progenitor cells. These cells divide to generate the different specialised cell types. Their divisions must be tightly controlled to ensure that our lungs always have the correct numbers and types of specialised cells. Misregulation of progenitor cell division results in changes to the lung structure which can contribute to important lung diseases, including asthma, emphysema and Chronic Obstructive Pulmonary Disease (COPD).

Our work uses the power of mouse genetics to understand the control of lung progenitor cell division in both growing and adult lungs. This fundamental research is essential for understanding the changes that can occur in our lungs as they become diseased, and for the development of cell-based therapies for lung repair.

Co-workers

Jane Brady • Jo-Anne Johnson • Florence Leroy • Marko Nikolic