title: Identification of a proximal progenitor population from murine fetal lungs with clonogenic and multilineage differentiation potential.
abstract: Lung development-associated diseases are major causes of morbidity and lethality in preterm infants and children. Access to the lung progenitor/stem cell populations controlling pulmonary development during embryogenesis and early postnatal years is essential to understand the molecular basis of such diseases. Using a Nkx2-1(mCherry) reporter mouse, we have identified and captured Nkx2-1-expressing lung progenitor cells from the proximal lung epithelium during fetal development. These cells formed clonal spheres in semisolid culture that could be maintained in vitro and demonstrated self-renewal and expansion capabilities over multiple passages. In-vitro-derived Nkx2-1-expressing clonal spheres differentiated into a polarized epithelium comprised of multiple cell lineages, including basal and secretory cells, that could repopulate decellularized lung scaffolds. Nkx2-1 expression thus defines a fetal lung epithelial progenitor cell population that can be used as a model system to study pulmonary development and associated pediatric diseases.
authors.affiliation: Program in Developmental and Stem Cell Biology, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto ON M5G 0A4, Canada.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Bilodeau
authors.affiliation: Program in Physiology and Experimental Medicine, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto ON M5G 0A4, Canada; Department of Physiology, University of Toronto, Toronto ON M5S 1A8, Canada.
authors.forename: Sharareh
authors.initials: S
authors.lastname: Shojaie
authors.affiliation: Program in Physiology and Experimental Medicine, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto ON M5G 0A4, Canada; Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto ON M5G 1X8, Canada.
authors.forename: Cameron
authors.initials: C
authors.lastname: Ackerley
authors.affiliation: Program in Physiology and Experimental Medicine, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto ON M5G 0A4, Canada; Department of Physiology, University of Toronto, Toronto ON M5S 1A8, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Post
authors.affiliation: Program in Developmental and Stem Cell Biology, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto ON M5S 1A8, Canada. Electronic address: janet.rossant@sickkids.ca.
authors.forename: Janet
authors.initials: J
authors.lastname: Rossant
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000196:embryology; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors