期刊
CELL STEM CELL
卷 22, 期 5, 页码 668-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2018.03.018
关键词
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资金
- NHLBI/NIH [4R00HL127181]
- Regeneration NeXT Initiative at Duke University
- CounterACT Program through the National Institute of Environmental Health Sciences of the NIH [U01ES017219]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R00HL127181] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [U01ES017219] Funding Source: NIH RePORTER
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 lumina! 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.
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