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

作　　者：Yanan Yang Guodong Deng Lili Qiao Hui Yuan Xiaohong Yu Lei Xu Shih-Hsin Lu Wei Jiang Xiying Yu 

机构地区：[1]Department of Etiology and Carcinogenesis,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China [2]State Key Laboratory of Molecular Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China [3]Beijing Key Laboratory for Carcinogenesis and Cancer Prevention,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China

出　　处：《Journal of Molecular Cell Biology》2022年第6期30-46,共17页分子细胞生物学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(NSFC)(81972572 to W.J.);the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-014 to Xiying Yu).

摘　　要：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.

关 键 词：esophageal stem cells hemidesmosomes Wnt signaling HOMEOSTASIS 

分 类 号：Q2[生物学—细胞生物学]