Department of Regenerative Medicine, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan.
J Hepatobiliary Pancreat Sci. 2012 Nov;19(6):587-93. doi: 10.1007/s00534-012-0544-4.
The liver is an essential organ that maintains vital activity through its numerous important functions. It has a unique capability of fully regenerating after injury. Regulating a balance between self-renewal and differentiation of hepatic stem cells that are resources for functional mature liver cells is required for maintenance of tissue homeostasis.
This review describes the characteristics of hepatic stem/progenitor cells and the regulatory mechanism of their self-renewal and differentiation capacity.
In liver organogenesis, undifferentiated hepatic stem/progenitor cells expand their pool by repeated self-renewal in the early stage of liver development and then differentiate into two different types of cell lineage, namely hepatocytes and cholangiocytes. Liver development is regulated by expression of stem cell transcription factors in a complex multistep process. Recent studies suggest that stem cells are maintained by integrative regulation of gene expression patterns related to self-renewal and differentiation by epigenetic mechanisms such as histone modification and DNA methylation.
Analysis of the proper regulatory mechanism of hepatic stem/progenitor cells is important for regenerative medicine that utilizes hepatic stem cells and for preventing liver cancer through clarification of the carcinogenetic mechanism involved in stem cell system failure.
肝脏是一个重要的器官，通过其众多重要的功能维持着生命活动。肝脏具有在受伤后完全再生的独特能力。调节肝干细胞的自我更新和分化能力之间的平衡，对于维持组织内稳态是必需的。肝干细胞是功能性成熟肝细胞的资源。
本综述描述了肝干细胞/祖细胞的特征以及调节其自我更新和分化能力的调控机制。
在肝发生过程中，未分化的肝干细胞/祖细胞在肝发育的早期通过反复自我更新来扩大其池，然后分化为两种不同类型的细胞谱系，即肝细胞和胆管细胞。肝发育是由干细胞转录因子的表达在一个复杂的多步骤过程中调节的。最近的研究表明，干细胞通过表观遗传机制（如组蛋白修饰和 DNA 甲基化）对与自我更新和分化相关的基因表达模式进行综合调控来维持。
分析肝干细胞/祖细胞的适当调控机制对于利用肝干细胞的再生医学以及通过阐明涉及干细胞系统故障的致癌机制来预防肝癌都很重要。
