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Cell Rep. 2015 Jul 7;12(1):90-101. doi: 10.1016/j.celrep.2015.06.011. Epub 2015 Jun 25.

Clonal Dynamics Reveal Two Distinct Populations of Basal Cells in Slow-Turnover Airway Epithelium.

Author information

1
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.
2
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.
3
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.
4
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Brussels 1070, Belgium.
5
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Brussels 1070, Belgium; Welbio, Université Libre de Bruxelles, Brussels 1070, Belgium.
6
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.

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.

PMID:
26119728
PMCID:
PMC4518462
DOI:
10.1016/j.celrep.2015.06.011
[Indexed for MEDLINE]
Free PMC Article
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