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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Tata, A; Kobayashi, Y; Chow, RD; Tran, J; Desai, A; Massri, AJ; McCord, TJ; Gunn, MD; Tata, PR

Published Date

  • May 3, 2018

Published In

Volume / Issue

  • 22 / 5

Start / End Page

  • 668 - 683.e6

PubMed ID

  • 29656943

Pubmed Central ID

  • 29656943

Electronic International Standard Serial Number (EISSN)

  • 1875-9777

Digital Object Identifier (DOI)

  • 10.1016/j.stem.2018.03.018

Language

  • eng

Conference Location

  • United States