Developmental Biology, Surgery
Keck School of Medicine
The Saban Research Institute
- Cancer Cell Biology
- Cell Cycle
- Growth & Proliferation
- Cell Death
- Developmental Biology
Research OverviewAlveolar Epithelial Cells: Development and Repair
We are investigating novel markers of a telomerase-positive, apoptosis resistant, proliferative population of lung eptithelial type 2 cells. These markers will be used as tools to purify putative alveolar stem/progenitor cells and determine their potential capacity to repopulate damaged lung.
During development, and following lung injury, a specialized population of alveolar epithelial cells (AEC) retain the capacity to proliferate. In adults, this ability is coupled with both survival and repopulation of the damaged alveolar epithelial surface. Preliminary experiments in our laboratory have shown that telomerase activity increases in developing AEC and in hyperoxic adult AEC during the proliferative repair phase following hyperoxic injury. These data suggest that a sub-population of proliferative AEC stem cells, present in fetal tissue, is also present in adult lung, and not only expands in response to injury, but may be intrinsically resistant to hyperoxic injury. We therefore hypothesize that alveolar epithelial stem cells that express telomerase resist hyperoxic damage, proliferate, and repopulate the damaged alveolar epithelium. In order to test this hypothesis, embryonic, fetal, and normal adult rat alveolar epithelial cells were assayed for telomerase expression, using immunohistochemistry, and activity, using the telomeric repeat amplification protocol (TRAP).
In addition, other markers of injury resistant AEC were investigated. We found that cells which lacked expression of the zonula adherens proteins E-cadherin and �-catenin made up the proliferating, non-apoptotic, telomerase positive compartment of the total adult AEC population. This change in surface marker expression may allow eventual separation of cells with progenitor phenotype from the heterogeneous AEC population.
The function of telomerase may be key to understanding how AEC stem cells develop and survive injury such as hyperoxia. This work may identify new targets for the design of novel rational approaches to augmentation of alveolar stem cell function in alveolar epithelial regeneration and repair, in both neonatal and adult human alveolar injury.