Journal article
Sox9 and Lef1 regulate the fate and behavior of airway glandular progenitors in response to injury
Stem Cells (Dayton, Ohio), Vol.40(8), pp.778-790
05/27/2022
DOI: 10.1093/stmcls/sxac038
PMCID: PMC9406614
PMID: 35639980
Abstract
Cartilaginous airways of larger mammals and the mouse trachea contain at least three well-established stem cell compartments including basal cells (BC) of the surface airway epithelium (SAE) and ductal and myoepithelial cells of the submucosal glands (SMG). Here we demonstrate that glandular Sox9-expressing progenitors capable of SAE repair decline with age in mice. Notably, Sox9-lineage glandular progenitors produced basal and ciliated cells in the SAE, but failed to produce secretory cells. Lef1 was required for glandular Sox9 lineage contribution to SAE repair and its deletion significantly reduced proliferation following injury. By contrast, in vivo deletion of Sox9 enhanced proliferation in both SAE and SMG progenitors shortly following injury, but these progenitors failed to proliferate in vitro in the absence of Sox9, similar to that previously shown for Lef1 deletion. In cystic fibrosis ferret airways, Sox9 expression inversely correlated with Ki67 proliferative marker expression in SMG and the SAE. Using in vitro and ex vivo models, we demonstrate that Sox9 is extinguished as glandular progenitors exit ducts and proliferate on the airway surface and that Sox9 is required for migration and proper differentiation of SMG, but not SAE, progenitors. We propose a model whereby Wnt/Lef1 and Sox9 signals differentially regulate the proliferative and migratory behavior of glandular progenitors, respectively.
Details
- Title: Subtitle
- Sox9 and Lef1 regulate the fate and behavior of airway glandular progenitors in response to injury
- Creators
- Vitaly Ievlev - University of IowaChandler Jensen-Cody - University of IowaThomas J Lynch - University of IowaAlbert C Pai - University of IowaSoo Park - University of IowaWeam Shahin - University of IowaKai Wang - University of IowaKalpaj R Parekh - University of IowaJohn F Engelhardt - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Stem Cells (Dayton, Ohio), Vol.40(8), pp.778-790
- DOI
- 10.1093/stmcls/sxac038
- PMID
- 35639980
- PMCID
- PMC9406614
- ISSN
- 1066-5099
- eISSN
- 1549-4918
- Grant note
- DOI: 10.13039/100000050, name: NHLBI, award: 75N92019R0014, P30 DK054759, R01 DK047967, R01 HL165404, R01 HL136370, T32 HL007638, K99HL155843
- Language
- English
- Date published
- 05/27/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Biostatistics; Radiation Oncology; Cardiothoracic Surgery; Internal Medicine
- Record Identifier
- 9984288758202771
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