Distinct spatiotemporally dynamic Wnt-secreting niches regulate proximal airway regeneration and aging

Details

• Alternative Title:
  Cell Stem Cell
• Personal Author:
  Aros, Cody J. ; Vijayaraj, Preethi ; Pantoja, Carla J. ; Bisht, Bharti ; Meneses, Luisa K. ; Sandlin, Jenna M. ; Tse, Jonathan A. ; Chen, Michelle W. ; Purkayastha, Arunima ; Shia, David W. ; Sucre, Jennifer M.S. ; Rickabaugh, Tammy M. ; Vladar, Eszter K. ; Paul, Manash K. ; Gomperts, Brigitte N.
• Description:
  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.
• Subjects:
  Aging Animals Beta Catenin Cell Differentiation Cell Proliferation Mice Mice, Transgenic Stem Cells Wnt Signaling Pathway
• Source:
  Cell Stem Cell. 27(3):413-429.e4
• Pubmed ID:
  32721381
• Pubmed Central ID:
  PMC7484054
• Document Type:
  Journal Article
• Funding:
  R21 MH119020/MH/NIMH NIH HHSUnited States/ ; T32 GM008042/GM/NIGMS NIH HHSUnited States/ ; R01 CA208303/CA/NCI NIH HHSUnited States/ ; UL1 TR000124/TR/NCATS NIH HHSUnited States/ ; R25 GM055052/GM/NIGMS NIH HHSUnited States/ ; P30 CA016042/CA/NCI NIH HHSUnited States/ ; F31 CA239655/CA/NCI NIH HHSUnited States/ ; T34 GM008563/GM/NIGMS NIH HHSUnited States/ ; T32 CA009056/CA/NCI NIH HHSUnited States/ ; U66 IP000597/IP/NCIRD CDC HHSUnited States/
• Volume:
  27
• Issue:
  3
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:64cf0c5aa5b11f03afaf1a22b4b11b1d9b2eae5dd69461666c711074fd7fbc22
• Download URL:
  https://stacks.cdc.gov/view/cdc/109535/cdc_109535_DS1.pdf
• File Type:
  [PDF - 3.67 MB ]