Journal article
Wnt Signaling Regulates Airway Epithelial Stem Cells in Adult Murine Submucosal Glands
Stem cells (Dayton, Ohio), Vol.34(11), pp.2758-2771
11/2016
DOI: 10.1002/stem.2443
PMCID: PMC5809158
PMID: 27341073
Abstract
Wnt signaling is required for lineage commitment of glandular stem cells (SCs) during tracheal submucosal gland (SMG) morphogenesis from the surface airway epithelium (SAE). Whether similar Wnt‐dependent processes coordinate SC expansion in adult SMGs following airway injury remains unknown. We found that two Wnt‐reporters in mice (BAT‐gal and TCF/Lef:H2B‐GFP) are coexpressed in actively cycling SCs of primordial glandular placodes and in a small subset of adult SMG progenitor cells that enter the cell cycle 24 hours following airway injury. At homeostasis, these Wnt reporters showed nonoverlapping cellular patterns of expression in the SAE and SMGs. Following tracheal injury, proliferation was accompanied by dynamic changes in Wnt‐reporter activity and the analysis of 56 Wnt‐related signaling genes revealed unique temporal changes in expression within proximal (gland‐containing) and distal (gland‐free) portions of the trachea. Wnt stimulation in vivo and in vitro promoted epithelial proliferation in both SMGs and the SAE. Interestingly, slowly cycling nucleotide label‐retaining cells (LRCs) of SMGs were spatially positioned near clusters of BAT‐gal positive serous tubules. Isolation and culture of tet‐inducible H2B‐GFP LRCs demonstrated that SMG LRCs were more proliferative than SAE LRCs and culture expanded SMG‐derived progenitor cells outcompeted SAE‐derived progenitors in regeneration of tracheal xenograft epithelium using a clonal analysis competition assay. SMG‐derived progenitors were also multipotent for cell types in the SAE and formed gland‐like structures in xenografts. These studies demonstrate the importance of Wnt signals in modulating SC phenotypes within tracheal niches and provide new insight into phenotypic differences of SMG and SAE SCs. Stem Cells 2016;34:2758–2771
Two distinct stem cell (SC) compartments in the mouse trachea include basal cells in the surface airway epithelium (SAE) and submucosal glands (SMGs). This research demonstrates that SCs from these two compartments have unique and overlapping properties that respond to dynamic changes in Wnt signaling following injury. Slowly cycling label‐retaining (LRC) SCs isolated from the SMGs had a greater proliferative capacity than SAE LRCs and glandular LRCs reside near Wnt‐active tubules. Isolated glandular SCs had a greater regenerative capacity to reconstitute a denuded tracheal xenograft than SAE SCs, and only glandular SCs formed gland‐like clones in xenografts and organoid cultures.
Details
- Title: Subtitle
- Wnt Signaling Regulates Airway Epithelial Stem Cells in Adult Murine Submucosal Glands
- Creators
- Thomas J Lynch - University of IowaPreston J Anderson - University of IowaWeiliang Xie - Molecular and Cellular Biology Program, University of IowaAdrianne K Crooke - University of IowaXiaoming Liu - University of IowaScott R Tyler - Molecular and Cellular Biology Program, University of IowaMeihui Luo - University of IowaDavid M Kusner - University of IowaYulong Zhang - University of IowaTraci Neff - University of Iowa Hospitals and ClinicsDaniel C Burnette - University of IowaKatherine S Walters - Central Microscopy Research FacilityMichael J Goodheart - University of Iowa Hospitals and ClinicsKalpaj R Parekh - University of Iowa Carver College of MedicineJohn F Engelhardt - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Stem cells (Dayton, Ohio), Vol.34(11), pp.2758-2771
- DOI
- 10.1002/stem.2443
- PMID
- 27341073
- PMCID
- PMC5809158
- ISSN
- 1066-5099
- eISSN
- 1549-4918
- Number of pages
- 15
- Grant note
- NIH grants (DK047967; HL051670) Carver Chair in Molecular Medicine University of Iowa Center for Gene Therapy (DK54759)
- Language
- English
- Date published
- 11/2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Surgery; Radiation Oncology; Obstetrics and Gynecology; Cardiothoracic Surgery; Internal Medicine
- Record Identifier
- 9984025442802771
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