The Role of Stem Cells During Lung Development and Disease
Morrisey, E. and B.L.M. Hogan (2010) Preparing for the First Breath: Genetic and Cellular mechanisms in Lung Development Dev. Cell 18: 8-23.
Rock, J., Onaitis, M.W., Rawlins, E.L., Lu, Y., Clark, C.P., Xue, Y., Randell, S.H., and B.L.M. Hogan (2009) Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc Natl. Acad. Sci. USA 106: 12771-12775.
Rawlins, E.L., Okubo, T., Xue, Y., Brass, D.M., Auten, R.L., Hasegawa, H., Wang, F. and B.L.M. Hogan (2009) The role of Scb1a1+ Clara cells in the long term maintenance and repair of lung airway but not alveolar epithelium. Cell Stem Cell 4: 525-534. Rawlins et al (2009) The Id2+ distal tip lung epithelium contains individual multipotent embryonic progenitor cells. Development 136: 3741-3745.
Dr. Hogan can you please tell us a bit about yourself, your career path over the years and how it has led you to the study of adult stem cells in the lung?
Moreover, to set up our video conference today can you please briefly define the nature of stem cells and their niche in the respiratory system during development and disease?
In your paper concerning the Id2+ positive distal tip lung epithelium, you discuss the lineage tracing in the pancreas that led researchers to suspect that multipotent progenitors were organized in the distal tip lung epithelium. What causes the progenitor cells to be restricted to this specific area? What specific elements in their niche signal them to replicate and differentiate?
In your 2009 Development paper, adult Id2+ cells were lineage-labeled to determine whether Id2+ multipotent progenitor cells persist in the adult. Although both Clara and ciliated cells were initially labeled in the bronchioles, 10 months after labeling, only labeled ciliated cells were found. However, a main finding in your 2009 Cell Stem Cell paper was that bronchiolar Clara cells do not just give rise to ciliated cells; they also self-renew. Thus, shouldn’t we expect to see Id2+-labeled Clara cells, as well as ciliated cells, in the bronchioles 10 months after labeling? Could two distinct subpopulations of Clara cells co-exist in the bronchioles, giving rise to this result?
Because your research largely focuses on adult stem cell development I am curious both as a scientist and individual where do you stand on the use of embryonic stem cells for research and future therapies? Is it still worthwhile to harvest embryonic stem cells to study their great potential or can adult stem cells ultimately meet the needs of both basic science and medicine?
Is the fact that there are two different types of cells (Clara and BASCs) supporting the upkeep and repair of lungs partly to blame for the aggressiveness and recurrence of lung cancer? If so, what does this mean for the promise of stem cells associated with the lungs and in future lung cancer therapies?
Your work confirmed cell mixing in the branching tip. Previous experiments by Shakya et al. also confirmed the cell mixing phenomenon in the kidney. Do you think other aspects of stem cell regulation in the lung can be applied to learn more about the kidney morphogenesis or the development of other adult stem cells and the organs they reside in?
Somatic cell reprogramming has significantly altered the landscape of stem cell research in recent years. Do you envision yourself using induced pluripotent stem (iPS) cells in future research? Do you feel that your own research has been impacted (with regard to funding, or in other ways) by iPS cell research?
Currently in your opinion what are the most pressing questions in the study of lung development and lung stem cell biology, and what steps is your lab taking to address these questions?