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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.

Original publication

DOI

10.1016/j.celrep.2015.06.011

Type

Journal article

Journal

Cell Rep

Publication Date

07/07/2015

Volume

12

Pages

90 - 101

Keywords

Animals, Cell Differentiation, Cell Lineage, Cell Proliferation, Epithelial Cells, Homeostasis, Mice, Mice, Inbred C57BL, Respiratory Mucosa