Tanimizu Naoki, Mitaka Toshihiro
Department of Tissue Development and Regeneration, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan.
Cold Spring Harb Perspect Biol. 2017 Aug 1;9(8):a027862. doi: 10.1101/cshperspect.a027862.
Tissue stem/progenitor cells supply multiple types of epithelial cells that eventually acquire specialized functions during organ development. In addition, three-dimensional (3D) tissue structures need to be established for organs to perform their physiological functions. The liver contains two types of epithelial cells, namely, hepatocytes and cholangiocytes, which are derived from hepatoblasts, fetal liver stem/progenitor cells (LPCs), in mid-gestation. Hepatocytes performing many metabolic reactions form cord-like structures, whereas cholangiocytes, biliary epithelial cells, form tubular structures called intrahepatic bile ducts. Analyses for human genetic diseases and mutant mice have identified crucial molecules for liver organogenesis. Functions of those molecules can be examined in in vitro culture systems where LPCs are induced to differentiate into hepatocytes or cholangiocytes. Recent technical advances have revealed 3D epithelial morphogenesis during liver organogenesis. Therefore, the liver is a good model to understand how tissue stem/progenitor cells differentiate and establish 3D tissue architectures during organ development.
组织干细胞/祖细胞可提供多种类型的上皮细胞，这些上皮细胞最终在器官发育过程中获得特定功能。此外，器官要发挥其生理功能，需要建立三维（3D）组织结构。肝脏包含两种上皮细胞，即肝细胞和胆管细胞，它们在妊娠中期由肝母细胞、胎儿肝干细胞/祖细胞（LPCs）分化而来。执行许多代谢反应的肝细胞形成索状结构，而胆管细胞，即胆管上皮细胞，则形成称为肝内胆管的管状结构。对人类遗传疾病和突变小鼠的分析已经确定了肝脏器官发生的关键分子。这些分子的功能可以在体外培养系统中进行研究，在该系统中，LPCs被诱导分化为肝细胞或胆管细胞。最近的技术进步揭示了肝脏器官发生过程中的3D上皮形态发生。因此，肝脏是了解组织干细胞/祖细胞在器官发育过程中如何分化并建立3D组织结构的良好模型。
