title: Clonal Dynamics Reveal Two Distinct Populations of Basal Cells in Slow-Turnover Airway Epithelium.
abstract: Epithelial lineages have been studied at cellular resolution in multiple organs that turn over rapidly. However, many epithelia, including those of the lung, liver, pancreas, and prostate, turn over slowly and may be regulated differently. We investigated the mouse tracheal epithelial lineage at homeostasis by using long-term clonal analysis and mathematical modeling. This pseudostratified epithelium contains basal cells and secretory and multiciliated luminal cells. Our analysis revealed that basal cells are heterogeneous, comprising approximately equal numbers of multipotent stem cells and committed precursors, which persist in the basal layer for 11 days before differentiating to luminal fate. We confirmed the molecular and functional differences within the basal population by using single-cell qRT-PCR and further lineage labeling. Additionally, we show that self-renewal of short-lived secretory cells is a feature of homeostasis. We have thus revealed early luminal commitment of cells that are morphologically indistinguishable from stem cells.
authors.affiliation: Wellcome Trust/CRUK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK; Wellcome Trust-MRC Stem Cell Institute University of Cambridge, Cambridge CB2 3EG, UK; Department of Pathology, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: Julie K
authors.initials: JK
authors.lastname: Watson
authors.affiliation: Wellcome Trust/CRUK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK; Wellcome Trust-MRC Stem Cell Institute University of Cambridge, Cambridge CB2 3EG, UK; Cavendish Laboratory, Department of Physics, J. J. Thomson Avenue, Cambridge CB3 0HE, UK.
authors.forename: Steffen
authors.initials: S
authors.lastname: Rulands
authors.affiliation: Wellcome Trust-MRC Stem Cell Institute University of Cambridge, Cambridge CB2 3EG, UK; Department of Haematology, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK; Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Wilkinson
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Brussels 1070, Belgium.
authors.forename: Aline
authors.initials: A
authors.lastname: Wuidart
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Brussels 1070, Belgium.
authors.forename: Marielle
authors.initials: M
authors.lastname: Ousset
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Brussels 1070, Belgium.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Van Keymeulen
authors.affiliation: Wellcome Trust-MRC Stem Cell Institute University of Cambridge, Cambridge CB2 3EG, UK; Department of Haematology, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK; Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Berthold
authors.initials: B
authors.lastname: Göttgens
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Brussels 1070, Belgium; Welbio, Université Libre de Bruxelles, Brussels 1070, Belgium.
authors.forename: Cédric
authors.initials: C
authors.lastname: Blanpain
authors.affiliation: Wellcome Trust/CRUK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK; Wellcome Trust-MRC Stem Cell Institute University of Cambridge, Cambridge CB2 3EG, UK; Cavendish Laboratory, Department of Physics, J. J. Thomson Avenue, Cambridge CB3 0HE, UK.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Simons
authors.affiliation: Wellcome Trust/CRUK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK; Wellcome Trust-MRC Stem Cell Institute University of Cambridge, Cambridge CB2 3EG, UK; Department of Pathology, University of Cambridge, Cambridge CB2 3EG, UK. Electronic address: e.rawlins@gurdon.cam.ac.uk.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Rawlins
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D006706:Homeostasis; D051379:Mice; D008810:Mice, Inbred C57BL; D020545:Respiratory Mucosa / Q000166:cytology*