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

Publication date: Available online 12 April 2018
Source:Cell Stem Cell
Author(s): Aleksandra Tata, Yoshihiko Kobayashi, Ryan D. Chow, Jasmine Tran, Avani Desai, Abdull J. Massri, Timothy J. McCord, Michael Dee Gunn, Purushothama Rao Tata
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.

Graphical abstract

Teaser

Airway submucosal glands are reservoirs of mucous and anti-microbial products that provide defense against microbes. Here, Tata and colleagues uncover a hidden reserve multipotent stem cell population in SMGs that can proliferate, migrate, and transdifferentiate to repair surface epithelium following injury through a SOX9-dependent transcriptional program.


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