title: Lung progenitors from lambs can differentiate into specialized alveolar or bronchiolar epithelial cells.
abstract: BACKGROUND
  Airways progenitors may be involved in embryogenesis and lung repair. The characterization of these important populations may enable development of new therapeutics to treat acute or chronic lung disease. In this study, we aimed to establish the presence of bronchioloalveolar progenitors in ovine lungs and to characterize their potential to differentiate into specialized cells.
  
  
  RESULTS
  Lung cells were studied using immunohistochemistry on frozen sections of the lung. Immunocytochemistry and flow cytometry were conducted on ex-vivo derived pulmonary cells. The bronchioloalveolar progenitors were identified by their co-expression of CCSP, SP-C and CD34. A minor population of CD34(pos)/SP-C(pos)/CCSP(pos) cells (0.33% ± 0.31) was present ex vivo in cell suspensions from dissociated lungs. Using CD34 magnetic positive-cell sorting, undifferentiated SP-C(pos)/CCSP(pos) cells were purified (>80%) and maintained in culture. Using synthetic media and various extracellular matrices, SP-C(pos)/CCSP(pos) cells differentiated into either club cells (formerly named Clara cells) or alveolar epithelial type-II cells. Furthermore, these ex vivo and in vitro derived bronchioloalveolar progenitors expressed NANOG, OCT4 and BMI1, specifically described in progenitors or stem cells, and during lung development.
  
  
  CONCLUSIONS
  We report for the first time in a large animal the existence of bronchioloalveolar progenitors with dual differentiation potential and the expression of specialized genes. These newly described cell population in sheep could be implicated in regeneration of the lung following lesions or in development of diseases such as cancers.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Archer
authors.forename: Alain
authors.initials: A
authors.lastname: Abi-Rizk
authors.forename: Sophie
authors.initials: S
authors.lastname: Desloire
authors.forename: Christine
authors.initials: C
authors.lastname: Dolmazon
authors.forename: Barbara
authors.initials: B
authors.lastname: Gineys
authors.forename: François
authors.initials: F
authors.lastname: Guiguen
authors.forename: Vincent
authors.initials: V
authors.lastname: Cottin
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Mornex
authors.affiliation: Université de Lyon, Lyon F-69007, France. caroline.leroux@univ-lyon1.fr.
authors.forename: Caroline
authors.initials: C
authors.lastname: Leroux
mesh_terms: D000818:Animals; D001980:Bronchi / Q000166:cytology* / Q000254:growth & development; D002454:Cell Differentiation / Q000502:physiology*; D005434:Flow Cytometry / Q000662:veterinary; D015870:Gene Expression / Q000502:physiology; D007150:Immunohistochemistry / Q000662:veterinary; D008168:Lung / Q000166:cytology* / Q000254:growth & development; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000254:growth & development; D037721:Pulmonary Surfactant-Associated Protein C / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000166:cytology / Q000254:growth & development; D012756:Sheep; D013234:Stem Cells / Q000502:physiology*
chemical_list: D037721:Pulmonary Surfactant-Associated Protein C