Wei-Hui Liu, Li-Na Ren, Tao Chen, Li-Ye Liu, Li-Jun Tang, General Surgery Center of PLA, Chengdu Military General Hospital, Chengdu 610083, Sichuan Province, China.
World J Gastroenterol. 2013 Nov 7;19(41):7032-41. doi: 10.3748/wjg.v19.i41.7032.
Except for the most organized mature hepatocytes, liver stem/progenitor cells (LSPCs) can differentiate into many other types of cells in the liver including cholangiocytes. In addition, LSPCs are demonstrated to be able to give birth to other kinds of extra-hepatic cell types such as insulin-producing cells. Even more, under some bad conditions, these LSPCs could generate liver cancer stem like cells (LCSCs) through malignant transformation. In this review, we mainly concentrate on the molecular mechanisms for controlling cell fates of LSPCs, especially differentiation of cholangiocytes, insulin-producing cells and LCSCs. First of all, to certificate the cell fates of LSPCs, the following three features need to be taken into account to perform accurate phenotyping: (1) morphological properties; (2) specific markers; and (3) functional assessment including in vivo transplantation. Secondly, to promote LSPCs differentiation, systematical attention should be paid to inductive materials (such as growth factors and chemical stimulators), progressive materials including intracellular and extracellular signaling pathways, and implementary materials (such as liver enriched transcriptive factors). Accordingly, some recommendations were proposed to standardize, optimize, and enrich the effective production of cholangiocyte-like cells out of LSPCs. At the end, the potential regulating mechanisms for generation of cholangiocytes by LSPCs were carefully analyzed. The differentiation of LSPCs is a gradually progressing process, which consists of three main steps: initiation, progression and accomplishment. It's the unbalanced distribution of affecting materials in each step decides the cell fates of LSPCs.
除了最有组织的成熟肝细胞外，肝干细胞/祖细胞（LSPCs）还可以在肝脏中分化为许多其他类型的细胞，包括胆管细胞。此外，LSPCs 被证明能够产生其他类型的肝外细胞类型，如产生胰岛素的细胞。更重要的是，在某些恶劣条件下，这些 LSPCs 可能通过恶性转化产生肝癌干细胞样细胞（LCSCs）。在这篇综述中，我们主要集中讨论控制 LSPC 细胞命运的分子机制，特别是胆管细胞、胰岛素产生细胞和 LCSCs 的分化。首先，为了证明 LSPCs 的细胞命运，需要考虑以下三个特征来进行准确的表型鉴定：（1）形态特征；（2）特异性标志物；（3）功能评估，包括体内移植。其次，为了促进 LSPCs 的分化，需要系统地关注诱导材料（如生长因子和化学刺激物）、渐进性材料，包括细胞内和细胞外信号通路，以及实施性材料（如肝富集转录因子）。因此，提出了一些建议来规范、优化和丰富 LSPCs 产生胆管样细胞的有效产量。最后，仔细分析了 LSPCs 产生胆管细胞的潜在调节机制。LSPCs 的分化是一个逐渐进展的过程，包括三个主要步骤：启动、进展和完成。是各步骤中影响物质的不平衡分布决定了 LSPCs 的细胞命运。
