Functional analysis of two distinct bronchiolar progenitors during lung injury and repair

Roxana M Teisanu, Huaiyong Chen, Keitaro Matsumoto, Jonathan Luke McQualter, Erin Potts, W Michael Foster, Ivan Bertoncello, Barry R Stripp

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67 Citations (Scopus)

Abstract

Air spaces of the mammalian lung are lined by a specialized epithelium that is maintained by endogenous progenitor cells. Within bronchioles, the abundance and distribution of progenitor cells that contribute to epithelial homeostasis change as a function of maintenance versus repair. What is unclear is whether functionally distinct progenitor pools or a single progenitor cell type maintain the epithelium, and how the behavior is regulated in normal or diseased states. To address these questions we applied fractionation methods for the enrichment of distal airway progenitors. We show that bronchiolar progenitor cells can be subdivided into two functionally distinct populations that differ in their susceptibility to injury and contribution to repair. The proliferative capacity of these progenitors is confirmed in a novel in vitro assay. We show that both populations give rise to colonies with a similar dependence on stromal cell interactions and regulation by TGFbeta. These findings provide additional insights into mechanisms of epithelial remodeling in the setting of chronic lung disease, and offer hope that pharmacologic interventions may be developed to mitigate tissue remodeling.
Original languageEnglish
Pages (from-to)794 - 803
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume44
Issue number6
DOIs
Publication statusPublished - 2011

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