Identification and characterization of stem cells in mammalian esophageal stratified squamous epithelia

Somatic stem cells are essential for the maintenance of tissue homeostasis. Despite its importance, how the esophageal stratified squamous epithelium executes its self-renewal and maintenance remains elusive. In this study, using 5-bromo-2'-deoxyuridine label-chase in rats in vivo and rat esoph...

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Published inJournal of molecular cell biology Vol. 14; no. 6
Main Authors Yang, Yanan, Deng, Guodong, Qiao, Lili, Yuan, Hui, Yu, Xiaohong, Xu, Lei, Lu, Shih-Hsin, Jiang, Wei, Yu, Xiying
Format Journal Article
LanguageEnglish
Published United States Oxford University Press 17.11.2022
Subjects
Animals
Carcinoma, Squamous Cell - metabolism
Cell Differentiation
Cell Proliferation
Epithelium - metabolism
Esophagus - metabolism
Mammals
Rats
Stem Cells - metabolism
Wnt Signaling Pathway
esophageal stem cells
homeostasis
hemidesmosomes
Wnt signaling
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Summary:Somatic stem cells are essential for the maintenance of tissue homeostasis. Despite its importance, how the esophageal stratified squamous epithelium executes its self-renewal and maintenance remains elusive. In this study, using 5-bromo-2'-deoxyuridine label-chase in rats in vivo and rat esophageal organoids in vitro together with genome-wide DNA methylation and single-cell RNA sequencing, we identified a slow-cycling/quiescent stem cell population that contained high levels of hemidesmosomes (HDs) and low levels of Wnt signaling localized spatially and randomly at the basal layer of the esophageal epithelium. Pseudotime cell trajectory analysis indicated that tissue cells originated from quiescent basal stem cells in the basal layer. Perturbations of HD component expression and/or Wnt signaling reduced the stem cell population in the basal layer of esophageal keratinocyte organoids, resulting in alterations in the organoid formation rate, size, morphogenesis, and proliferation-differentiation homeostasis. Furthermore, not only high levels of HDs and low levels of Wnt signaling but also an interplay between HD and Wnt signaling defined the stem cells of the basal layer. Hence, HDs and Wnt signaling are critical determinants for defining the stem cells of the basal layer required for tissue homeostasis in mammalian esophagi.
ISSN:1674-2788
1759-4685
DOI:10.1093/jmcb/mjac038