期刊
CELL STEM CELL
卷 27, 期 3, 页码 413-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2020.06.019
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资金
- UCLA Medical Scientist Training Program (NIH NIGMS) [GM008042]
- NIH/NCI NRSA Predoctoral F31 Diversity Fellowship [F31CA239655]
- UCLA Eli & Edythe Broad Center of Regenerative Medicine (BSCRC) and Stem Cell Research Training Grant
- T32 National Research Service Award in Tumor Cell Biology [CA009056]
- NIH/NCI [R01CA208303]
- Tobacco-Related Disease Research Program (TRDRP) High Impact Pilot Research Award (HIPRA) [26IP-0036]
- TRDRP HIPRA [29IP0597]
- UCLA Jonsson Comprehensive Cancer Center (JCCC) STOP Cancer Award
- Ablon Research Scholars Award
- UCLA Maximizing Student Development Award (NIH NIGMS) [R25GM055052]
- National Center for Advancing Translational Sciences (NCATS) UCLA CTSI grant [UL1TR000124]
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/beta-catenin within ABSCs was essential for proliferation post-injury in vivo. ABSC-derived Wnt ligand production was dispensable for epithelial proliferation. Instead, the PDGFR alpha(+) 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 beta-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.
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