Determination of the Role of Endothelial Cells and Mesenchymal Cells in Regulating Lung

Tissue regenerative potential is governed by environmental signals from the surrounding niche, including mesenchymal progenitors and vascular endothelium, which may directly influence the activity of organ-specific stem cells. In this proposal, we will investigate the mechanisms by which these stromal elements regulate stem/progenitor cell activity in normal lung to reveal the mechanisms controlling lung homeostasis and repair. These studies will make use of sensitive and specific cell sorting paradigms to isolate lung stem cells, and will develop analogous, novel strategies to discriminate the stromal elements that regulate their function. Specifically, we will first determine the ability of endothelial cells (ECs) and fibrogenic/adipogenic progenitor
cells (FAPs) from lung tissue to support the self-renewal and differentiation of the distal lung stem and progenitor cells, bronchio-alveolar stem cells (BASCs) and alveolar type II cells (AT2) in culture systems. Molecules important in EC and FAP regulation of BASCs and AT2 cells will be identified with biochemical approaches. Second, we will examine the effect of EC abrogation on bronchiolar and alveolar epithelial cell injury repair using genetic and chemical maniupulations. This synergistic combination of in vitro co-culture and in vivo injury methods, techniques with which the PI’s labs have extensive expertise and supportive preliminary data, will allow us to investigate the cellular and molecular processes that mediate the regulatory interactions of lung stem cells with their niche. The ultimate elucidation of mechanisms through which niches control stem cell function will aid in the development of novel therapeutic targeting for lung diseases.

Copyright ©2013 NHLBI Progenitor Cell Biology Consortium.

University of Maryland School of Medicine logo

National Heart Blood and Lung Institute logo