Pinto Daniel, Clevers Hans
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, 3584 CT Utrecht, The Netherlands.
Exp Cell Res. 2005 Jun 10;306(2):357-63. doi: 10.1016/j.yexcr.2005.02.022. Epub 2005 Apr 7.
The intestinal epithelium represents a very attractive experimental model for the study of integrated key cellular processes such as proliferation and differentiation. The tissue is subjected to a rapid and perpetual self-renewal along the crypt-villus axis. Renewal requires division of multipotent stem cells, still to be morphologically identified and isolated, followed by transit amplification, and differentiation of daughter cells into specialized absorptive and secretory cells. Our understanding of the crucial role played by the Wnt/beta-catenin signaling pathway in controlling the fine balance between cell proliferation and differentiation in the gut has been significantly enhanced in recent years. Mutations in some of its components irreversibly lead to carcinogenesis in humans and in mice. Here, we discuss recent advances related to the Wnt/beta-catenin signaling pathway in regulating intestinal stem cells, homeostasis, and cancer. We emphasize how Wnt signaling is able to maintain a stem cell/progenitor phenotype in normal intestinal crypts, and to impose a very similar phenotype onto colorectal adenomas.
肠道上皮是研究增殖和分化等关键细胞整合过程的极具吸引力的实验模型。该组织沿隐窝-绒毛轴经历快速且持续的自我更新。更新需要多能干细胞进行分裂（这些干细胞仍有待从形态学上进行识别和分离），随后是过渡性增殖，以及子细胞分化为特化的吸收性和分泌性细胞。近年来，我们对Wnt/β-连环蛋白信号通路在控制肠道细胞增殖和分化之间精细平衡中所起关键作用的理解有了显著增强。其某些组分的突变会在人类和小鼠中不可逆地导致癌变。在此，我们讨论与Wnt/β-连环蛋白信号通路在调节肠道干细胞、内环境稳定和癌症方面相关的最新进展。我们着重阐述Wnt信号如何能够在正常肠道隐窝中维持干细胞/祖细胞表型，并在结直肠腺瘤中赋予非常相似的表型。
