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Cell Stem Cell. 2018 May 3;22(5):668-683.e6. doi: 10.1016/j.stem.2018.03.018. Epub 2018 Apr 12.

Myoepithelial Cells of Submucosal Glands Can Function as Reserve Stem Cells to Regenerate Airways after Injury.

Author information

1
Department of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA.
2
Department of Genetics, Systems Biology Institute, Medical Scientist Training Program, Yale University School of Medicine, New Haven, CT 06520, USA.
3
Department of Medicine, Division of Cardiology, Duke University School of Medicine, Durham, NC 27710, USA.
4
Department of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA; Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA; Regeneration Next, Duke University, Durham, NC 27710, USA. Electronic address: purushothamarao.tata@duke.edu.

Abstract

Cells demonstrate plasticity following injury, but the extent of this phenomenon and the cellular mechanisms involved remain underexplored. Using single-cell RNA sequencing (scRNA-seq) and lineage tracing, we uncover that myoepithelial cells (MECs) of the submucosal glands (SMGs) proliferate and migrate to repopulate the airway surface epithelium (SE) in multiple injury models. Specifically, SMG-derived cells display multipotency and contribute to basal and luminal cell types of the SMGs and SE. Ex vivo expanded MECs have the potential to repopulate and differentiate into SE cells when grafted onto denuded airway scaffolds. Significantly, we find that SMG-like cells appear on the SE of both extra- and intra-lobular airways of large animal lungs following severe injury. We find that the transcription factor SOX9 is necessary for MEC plasticity in airway regeneration. Because SMGs are abundant and present deep within airways, they may serve as a reserve cell source for enhancing human airway regeneration.

KEYWORDS:

airway regeneration; cellular plasticity; multipotent stem cells; myoepithelial cells; reserve stem cells; single-cell RNA sequencing; submucosal gland stem cells

PMID:
29656943
PMCID:
PMC5935539
[Available on 2019-05-03]
DOI:
10.1016/j.stem.2018.03.018

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