TY - JOUR
T1 - Distinct Spatiotemporally Dynamic Wnt-Secreting Niches Regulate Proximal Airway Regeneration and Aging
AU - Aros, Cody J.
AU - Vijayaraj, Preethi
AU - Pantoja, Carla J.
AU - Bisht, Bharti
AU - Meneses, Luisa K.
AU - Sandlin, Jenna M.
AU - Tse, Jonathan A.
AU - Chen, Michelle W.
AU - Purkayastha, Arunima
AU - Shia, David W.
AU - Sucre, Jennifer M.S.
AU - Rickabaugh, Tammy M.
AU - Vladar, Eszter K.
AU - Paul, Manash K.
AU - Gomperts, Brigitte N.
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/9/3
Y1 - 2020/9/3
N2 - Our understanding of dynamic interactions between airway basal stem cells (ABSCs) and their signaling niches in homeostasis, injury, and aging remains elusive. Using transgenic mice and pharmacologic studies, we found that Wnt/β-catenin within ABSCs was essential for proliferation post-injury in vivo. ABSC-derived Wnt ligand production was dispensable for epithelial proliferation. Instead, the PDGFRα+ lineage in the intercartilaginous zone (ICZ) niche transiently secreted Wnt ligand necessary for ABSC proliferation. Strikingly, ABSC-derived Wnt ligand later drove early progenitor differentiation to ciliated cells. We discovered additional changes in aging, as glandular-like epithelial invaginations (GLEIs) derived from ABSCs emerged exclusively in the ICZ of aged mice and contributed to airway homeostasis and repair. Further, ABSC Wnt ligand secretion was necessary for GLEI formation, and constitutive activation of β-catenin in young mice induced their formation in vivo. Collectively, these data underscore multiple spatiotemporally dynamic Wnt-secreting niches that regulate functionally distinct phases of airway regeneration and aging.
AB - Our understanding of dynamic interactions between airway basal stem cells (ABSCs) and their signaling niches in homeostasis, injury, and aging remains elusive. Using transgenic mice and pharmacologic studies, we found that Wnt/β-catenin within ABSCs was essential for proliferation post-injury in vivo. ABSC-derived Wnt ligand production was dispensable for epithelial proliferation. Instead, the PDGFRα+ lineage in the intercartilaginous zone (ICZ) niche transiently secreted Wnt ligand necessary for ABSC proliferation. Strikingly, ABSC-derived Wnt ligand later drove early progenitor differentiation to ciliated cells. We discovered additional changes in aging, as glandular-like epithelial invaginations (GLEIs) derived from ABSCs emerged exclusively in the ICZ of aged mice and contributed to airway homeostasis and repair. Further, ABSC Wnt ligand secretion was necessary for GLEI formation, and constitutive activation of β-catenin in young mice induced their formation in vivo. Collectively, these data underscore multiple spatiotemporally dynamic Wnt-secreting niches that regulate functionally distinct phases of airway regeneration and aging.
UR - https://www.scopus.com/pages/publications/85089400103
UR - https://www.scopus.com/inward/citedby.url?scp=85089400103&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2020.06.019
DO - 10.1016/j.stem.2020.06.019
M3 - Article
C2 - 32721381
AN - SCOPUS:85089400103
SN - 1934-5909
VL - 27
SP - 413-429.e4
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 3
ER -