Novartis Institutes for BioMedical Research, Novartis Pharma AGBaselSwitzerland.
Gene Expr. 2020 Nov 11;20(2):119-124. doi: 10.3727/105221620X16007982788168. Epub 2020 Sep 22.
WNT/-catenin signaling promotes stemness, proliferation, and cell fate decisions in various tissue stem cell compartments, which maintain organs with a high turnover of cells (e.g., skin, stomach, and gut). Thus, the -catenin target genes AXIN2 and LGR5 are widely considered as tissue stem cell markers. In contrast, AXIN2 and LGR5 are expressed in pericentral hepatocytes, which do not show overt proliferation during liver homeostasis. Given the low hepatocyte turnover, the liver does not require constant high rates of proliferation, whereas WNT/-catenin signaling is critical for metabolic zonation. Yet, WNT/-catenin pathway upregulation, including AXIN2 and LGR5 induction in hepatocytes throughout the liver, enables hepatocyte regeneration in response to various injuries. In this brief review, I discuss the role of WNT/-catenin signaling in controlling metabolic zonation and the conundrum around pericentral hepatocytes that have been proposed as liver stem cells.
WNT/-catenin 信号通路促进各种组织干细胞隔室中的干性、增殖和细胞命运决定，这些隔室维持着细胞高周转率的器官（例如皮肤、胃和肠道）。因此，-catenin 的靶基因 AXIN2 和 LGR5 被广泛认为是组织干细胞标志物。相比之下，AXIN2 和 LGR5 表达在中央周肝细胞中，在肝内稳态期间这些细胞没有明显的增殖。由于肝细胞周转率低，肝脏不需要持续的高增殖率，而 WNT/-catenin 信号通路对于代谢分区至关重要。然而，WNT/-catenin 信号通路的上调，包括在整个肝脏中的肝细胞中诱导 AXIN2 和 LGR5，使得肝细胞能够对各种损伤做出再生反应。在这篇简短的综述中，我讨论了 WNT/-catenin 信号通路在控制代谢分区中的作用，以及中央周肝细胞作为肝干细胞的难题。
