Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction

Adam Giangreco, Susan D Reynolds, Barry R Stripp

Research output: Contribution to journalArticlepeer-review

466 Citations (Scopus)


Cellular mechanisms contributing to renewal of terminal bronchioles remain poorly defined. Our previous studies identified pollutant-resistant Clara cell secretory protein (CCSP)-expressing stem cells that localize to the neuroepithelial body (NEB) and contribute to renewal of the proximal bronchiolar epithelium. However, activation of NEB-associated stem cells is unlikely to contribute to renewal of terminal bronchiolar epithelium because of the paucity of NEBs at this location. Goals of this study were to determine the location and properties of cells contributing to renewal of terminal bronchioles after Clara cell depletion. Pollutant-resistant CCSP-expressing cells were identified that localized to the bronchoalveolar duct junction (BADJ) and contribute to restoration of a phenotypically diverse epithelium. CCSP-expressing cells comprise the predominant proliferative population in initial terminal bronchiolar repair and include a population of label-retaining cells suggesting that they maintain characteristics of a stem cell population. Furthermore, immunohistochemical co-localization studies involving CCSP and the NEB-specific marker calcitonin gene-related peptide indicate that BADJ-associated CCSP-expressing stem cells function independently of NEB microenvironments. These studies identify a BADJ-associated, NEB-independent, CCSP-expressing stem cell population in terminal bronchioles and support the notion that regiospecific stem cell niches function to maintain epithelial diversity after injury.

Original languageEnglish
Pages (from-to)173-82
Number of pages10
JournalAmerican Journal of Pathology
Issue number1
Publication statusPrint publication - Jul 2002
Externally publishedYes


  • Animals
  • Bronchi/cytology
  • Calcitonin Gene-Related Peptide/metabolism
  • Cell Cycle/physiology
  • Cell Division
  • Drug Resistance
  • Male
  • Mice
  • Mice, Inbred Strains
  • Naphthalenes/pharmacology
  • Neurosecretory Systems/cytology
  • Proteins/drug effects
  • Pulmonary Alveoli/cytology
  • RNA, Messenger/metabolism
  • Regeneration/physiology
  • Respiratory Mucosa/cytology
  • Respiratory Physiological Phenomena
  • Stem Cells/cytology
  • Uteroglobin


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