Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Nat Genet. 2011 Jan;43(1):34-41. doi: 10.1038/ng.722. Epub 2010 Nov 28.
The liver and exocrine pancreas share a common structure, with functioning units (hepatic plates and pancreatic acini) connected to the ductal tree. Here we show that Sox9 is expressed throughout the biliary and pancreatic ductal epithelia, which are connected to the intestinal stem-cell zone. Cre-based lineage tracing showed that adult intestinal cells, hepatocytes and pancreatic acinar cells are supplied physiologically from Sox9-expressing progenitors. Combination of lineage analysis and hepatic injury experiments showed involvement of Sox9-positive precursors in liver regeneration. Embryonic pancreatic Sox9-expressing cells differentiate into all types of mature cells, but their capacity for endocrine differentiation diminishes shortly after birth, when endocrine cells detach from the epithelial lining of the ducts and form the islets of Langerhans. We observed a developmental switch in the hepatic progenitor cell type from Sox9-negative to Sox9-positive progenitors as the biliary tree develops. These results suggest interdependence between the structure and homeostasis of endodermal organs, with Sox9 expression being linked to progenitor status.
肝脏和外分泌胰腺具有共同的结构，功能单位（肝板和胰腺腺泡）连接到导管树。在这里，我们表明 Sox9 在整个胆道和胰腺导管上皮中表达，这些上皮与肠干细胞区相连。基于 Cre 的谱系追踪表明，成年肠细胞、肝细胞和胰腺腺泡细胞从 Sox9 表达的祖细胞中得到生理性供应。谱系分析和肝损伤实验的组合表明 Sox9 阳性前体细胞参与肝再生。胚胎胰腺 Sox9 表达细胞分化为所有类型的成熟细胞，但它们的内分泌分化能力在出生后不久就会减弱，此时内分泌细胞从导管的上皮衬里分离出来并形成胰岛。我们观察到，随着胆管树的发育，肝祖细胞类型从 Sox9 阴性转变为 Sox9 阳性祖细胞。这些结果表明内胚层器官的结构和动态平衡相互依存，Sox9 表达与祖细胞状态相关。
