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

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

Watson JK1, Rulands S2, Wilkinson AC3, Wuidart A4, Ousset M4, Van Keymeulen A4, Göttgens B3, Blanpain C5, Simons BD2, Rawlins EL6.

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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

PMID 26119728