[PDF][PDF] Submucosal gland myoepithelial cells are reserve stem cells that can regenerate mouse tracheal epithelium

TJ Lynch, PJ Anderson, PG Rotti, SR Tyler, AK Crooke… - Cell stem cell, 2018 - cell.com
TJ Lynch, PJ Anderson, PG Rotti, SR Tyler, AK Crooke, SH Choi, DT Montoro, CL Silverman…
Cell stem cell, 2018cell.com
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 …
Summary
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.
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