Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine
Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine
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DOI：
10.1038/ng.722
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发表时间：
2011-01-01
期刊：
影响因子：
30.8
通讯作者：
Uemoto, Shinji
中科院分区：
文献类型：
--
作者：
Furuyama, Kenichiro;Kawaguchi, Yoshiya;Uemoto, Shinji
肝脏和外分泌胰腺共享一个共同的结构，功能单位(肝板和胰腺腺泡)连接到导管树。在这里，我们发现Sox9表达于连接到肠道干细胞区域的胆管和胰管上皮细胞。基于Cre的谱系追踪表明，成年肠道细胞、肝细胞和胰腺腺泡细胞是由表达Sox9的祖细胞生理上提供的。谱系分析和肝损伤实验相结合表明，SOX9阳性前体参与了肝再生。胚胎胰腺中表达Sox9的细胞可分化为所有类型的成熟细胞，但其内分泌分化能力在出生后不久就会减弱，此时内分泌细胞会从导管的上皮衬里分离出来，形成朗格汉斯胰岛。随着胆管树的发育，我们观察到肝祖细胞类型从SOX9阴性到SOX9阳性的发育转换。这些结果表明，内胚层器官的结构和动态平衡之间相互依赖，Sox9的表达与祖细胞状态有关。
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.