MRC Research Fellow
Project: Stem and progenitor cells in the mammalian lung
Tennis Court Road
We have previously shown that in the embryonic lung there is a population of Id2+ multipotent epithelial progenitor cells located at the distal tips of the budding epithelium. The developmental potential, or competence, of these cells changes during embryogenesis. At the same time the cells undergo a change in gene expression pattern. Currently we are testing the function of some of these genes, which are hypothesized to regulate the sequence of descendents produced by the progenitors. The identity of the epithelial stem and progenitor cells in the postnatal lung remains controversial. Our previous work has shown that each anatomical region (trachea, bronchioles, alveoli) has its own progenitor cell population and that the behaviour of these progenitors can change in response to local conditions. Our current postnatal work focuses on:
- Better characterizing the adult lung progenitor cells. This includes testing whether progenitor cell behaviour is widespread or there are stem cells.
- Understanding the genetic regulation of the progenitors under several different physiologically-relevant conditions. In particular, we are focusing on genes that are hypothesized to control the decision to self-renew or differentiate.
Our ability to breathe at birth requires that during embryonic development our lungs make many types of specialized 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 specialized cell types. Their divisions must be tightly controlled to ensure that our lungs always have the correct numbers and types of specialized cells. Misregulation of progenitor cell division results in changes to the lung structure which can contribute to important lung diseases, including asthma, emphysema and COPD (Chronic Obstructive Pulmonary Disease). 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.
- Group members:
Gayan Balasooriya, Christoph Budjan, Simon Gerber, Usua Laresgoiti, Jo-Ann Johnson, Chandirka Rao.
- Rawlins E.L., Clark C.P., Xue Y., and Hogan B.L.M. The Id2 distal tip lung epithelium contains individual multipotent embryonic progenitor cells (2009) Development 136 3741-3745
- Rawlins E.L, Okubo T., Xue Y., Brass D.M., Auten R.L., Hasegawa H., Wang F. and Hogan B.L.M. (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
- Rawlins E.L. and Hogan B.L.M. (2008) Ciliated epithelial cell lifespan in the mouse trachea and lung. American Journal of Physiology: Lung Cell Molecular Physiology 295, L231-234
- Rawlins E.L., Ostrowski L.E., Randell S.H. and Hogan B.L.M. (2007) Lung development and repair: contribution of the ciliated lineage. Proc Natl Acad Sci USA 104, 410-417
- Onaitis M., D'Amico T.A., Clark C., Guinney J., Harpole D.H., and Rawlins E.L. A 10-gene progenitor cell signature predicts prognosis in lung adenocarcinoma. Annals of Thoracic Surgery, 2011 91 1046-50.