Deletion of Pten expands lung epithelial progenitor pools and confers resistance to airway injury

Caterina Tiozzo, Stijn De Langhe, Mingke Yu, Vedang A. Londhe, Gianni Carraro, Min Li, Changgong Li, Yiming Xing, Stewart Anderson, Zea Borok, Saverio Bellusci, Parviz Minoo

Research output: Contribution to journalArticlepeer-review


Rationale: Pten is a tumor-suppressor gene involved in stem cell homeostasis and tumorigenesis. In mouse, Pten expression is ubiquitous and begins as early as 7 days of gestation. Pten-/- mouse embryos die early during gestation indicating a critical role for Pten in embryonic development. Objectives: To test the role of Pten in lung development and injury. Methods: We conditionally deleted Pten throughout the lung epithelium by crossing Pten flox/flox with Nkx2.1-cre driver mice. The resulting Pten Nkx2.1-cre mutants were analyzed for lung defects and response to injury. Measurements and Main Results: PtenNkx2.1-cre embryonic lungs showed airway epithelial hyperplasia with no branching abnormalities. In adult mice, PtenNkx2.1-cre lungs exhibit increasedprogenitor cell pools composed of basal cells in the trachea, CGRP/CC10 double-positive neuroendocrine cells in the bronchi, and CC10/SPC double-positive cells at the bronchioalveolar duct junctions. Pten deletion affected differentiation of various lung epithelial cell lineages, with a decreased number of terminally differentiated cells. Over time, PtenNxk2.1-cre epithelial cells residing in the bronchioalveolar duct junctions underwent proliferation and formed uniform masses, supporting the concept that the cells residing in this distal niche may also be the source of procarcinogenic stem cells. Finally, increased progenitor cells in all the lung compartments conferred an overall selective advantage to naphthalene injury compared with wild-type control mice. Conclusions: Pten has a pivotal role in lung stem cell homeostasis, cell differentiation, and consequently resistance to lung injury.

Original languageEnglish (US)
Pages (from-to)701-712
Number of pages12
JournalAmerican journal of respiratory and critical care medicine
Issue number8
StatePublished - Oct 15 2009


  • Injury
  • Lung progenitor cells
  • Pten

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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