PDF(Pubmed)
Abstract：
The extrahepatic branches of the biliary tree have glands that connect to the surface epithelium through narrow pits. The duct epithelia undergo homeostatic renewal, yet the identity and multiplicity of cells that maintain this tissue is unknown. Using marker-free and targeted clonal fate mapping in mice, we provide evidence that the extrahepatic bile duct is compartmentalized. Pit cholangiocytes of extramural glands renewed the surface epithelium, whereas basally oriented cholangiocytes maintained the gland itself. In contrast, basally positioned cholangiocytes replenished the surface epithelium in mural glands. Single-cell sequencing identified genes enriched in the base and surface epithelial populations, with trajectory analysis showing graded gene expression between these compartments. Epithelia were plastic, changing cellular identity upon fasting and refeeding. Gain of canonical Wnt signaling caused basal cell expansion, gastric chief cell marker expression, and a decrease in surface epithelial markers. Our results identify the cellular hierarchy governing extrahepatic biliary epithelial renewal.
摘要：
胆道树的肝外分支具有通过狭窄的凹坑连接到表面上皮的腺体。导管上皮经历稳态更新，然而，维持这种组织的细胞的身份和多样性是未知的。在小鼠中使用无标记和有针对性的克隆命运作图，我们提供的证据表明肝外胆管是分隔的。壁外腺的坑胆管细胞更新表面上皮，而基底定向的胆管细胞维持腺体本身。相比之下,位于基底的胆管细胞补充了壁腺的表面上皮。单细胞测序鉴定了富含碱基和表面上皮群体的基因，轨迹分析显示这些区室之间的基因表达分级。上皮是可塑的，在禁食和重新喂食时改变细胞身份。经典Wnt信号的增益导致基底细胞扩增，胃主细胞标志物表达，表面上皮标志物减少。我们的结果确定了控制肝外胆管上皮更新的细胞层次。
