Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate Mouse Tracheal Epithelium

Publication date: Available online 12 April 2018
Source:Cell Stem Cell
Author(s): Thomas J. Lynch, Preston J. Anderson, Pavana G. Rotti, Scott R. Tyler, Adrianne K. Crooke, Soon H. Choi, Daniel T. Montoro, Carolyn L. Silverman, Weam Shahin, Rui Zhao, Chandler W. Jensen-Cody, Andrea Adamcakova-Dodd, T. Idil Apak Evans, Weiliang Xie, Yulong Zhang, Hongmei Mou, B. Paul Herring, Peter S. Thorne, Jayaraj Rajagopal, Charles Yeaman, Kalpaj R. Parekh, John F. Engelhardt
The mouse trachea is thought to contain two distinct stem cell compartments that contribute to airway repair—basal cells in the surface airway epithelium (SAE) and an unknown submucosal gland (SMG) cell type. Whether a lineage relationship exists between these two stem cell compartments remains unclear. Using lineage tracing of glandular myoepithelial cells (MECs), we demonstrate that MECs can give rise to seven cell types of the SAE and SMGs following severe airway injury. MECs progressively adopted a basal cell phenotype on the SAE and established lasting progenitors capable of further regeneration following reinjury. MECs activate Wnt-regulated transcription factors (Lef-1/TCF7) following injury and Lef-1 induction in cultured MECs promoted transition to a basal cell phenotype. Surprisingly, dose-dependent MEC conditional activation of Lef-1 in vivo promoted self-limited airway regeneration in the absence of injury. Thus, modulating the Lef-1 transcriptional program in MEC-derived progenitors may have regenerative medicine applications for lung diseases.

Graphical abstract

Teaser

Following severe injury to the surface airway epithelium (SAE), Wnt signals activate myoepithelial cells in the submucosal glands (SMGs) to function as reserve stem cells for multipotent basal cells in the SAE and other SMG cell types. Lef-1 activation induces the myoepithelial cell regenerative response and a basal cell-like phenotype.


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