Kalabis Jiri, Oyama Kenji, Okawa Takaomi, Nakagawa Hiroshi, Michaylira Carmen Z, Stairs Douglas B, Figueiredo Jose-Luiz, Mahmood Umar, Diehl J Alan, Herlyn Meenhard, Rustgi Anil K
Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
J Clin Invest. 2008 Dec;118(12):3860-9. doi: 10.1172/JCI35012. Epub 2008 Nov 6.
The esophageal epithelium is a prototypical stratified squamous epithelium that exhibits an exquisite equilibrium between proliferation and differentiation. After basal cells proliferate, they migrate outward toward the luminal surface, undergo differentiation, and eventually slough due to apoptosis. The identification and characterization of stem cells responsible for the maintenance of the esophageal epithelium remains elusive. Here, we employed Hoechst dye extrusion and BrdU label-retaining assays to identify in mice a potential esophageal stem cell population that localizes to the basal cell compartment. The self-renewing capacity of this population was characterized using a clonogenic assay and a 3D organotypic culture model. The putative esophageal stem cells were also capable of epithelial reconstitution in vivo in direct esophageal epithelial injury models. In both the 3D organotypic culture and direct mucosal injury models, the putative stem cells gave rise to undifferentiated and differentiated cells. These studies therefore provide a basis for understanding the regenerative capacity and biology of the esophageal epithelium when it is faced with injurious insults.
食管上皮是一种典型的复层鳞状上皮,在增殖和分化之间呈现出精妙的平衡。基底细胞增殖后,会向管腔表面向外迁移,进行分化,最终因凋亡而脱落。负责维持食管上皮的干细胞的鉴定和特征仍不清楚。在这里,我们采用Hoechst染料排除法和BrdU标记保留试验,在小鼠中鉴定出一个定位于基底细胞区室的潜在食管干细胞群体。使用克隆形成试验和三维器官型培养模型对该群体的自我更新能力进行了表征。在直接食管上皮损伤模型中,推定的食管干细胞在体内也能够进行上皮重建。在三维器官型培养和直接黏膜损伤模型中,推定的干细胞都能产生未分化和分化的细胞。因此,这些研究为理解食管上皮在面临损伤性刺激时的再生能力和生物学特性提供了基础。