Department of Medical Genetics, University of Antwerp, Prins Boudewijnlaan 43, 2650, Edegem, Antwerp, Belgium.
Stem Cell Rev Rep. 2014 Apr;10(2):207-29. doi: 10.1007/s12015-013-9486-8.
Wnt signaling determines major developmental processes in the embryonic state and regulates maintenance, self-renewal and differentiation of adult mammalian tissue stem cells. Both β-catenin dependent and independent Wnt pathways exist, and both affect stem cell fate in developing and adult tissues. In this review, we debate the response to Wnt signal activation in embryonic stem cells and human, adult stem cells of mesenchymal, hematopoetic, intestinal, gastric, epidermal, mammary and neural lineages, and discuss the need for Wnt signaling in these cell types. Due to the vital actions of Wnt signaling in developmental and maintenance processes, deregulation of the pathway can culminate into a broad spectrum of developmental and genetic diseases, including cancer. The way in which Wnt signals can feed tumors and maintain cancer stem stells is discussed as well. Manipulation of Wnt signals both in vivo and in vitro thus carries potential for therapeutic approaches such as tissue engineering for regenerative medicine and anti-cancer treatment. Although many questions remain regarding the complete Wnt signal cell-type specific response and interplay of Wnt signaling with pathways such as BMP, Hedgehog and Notch, we hereby provide an overview of current knowledge on Wnt signaling and its control over human stem cell fate.
Wnt 信号决定了胚胎状态下的主要发育过程，并调节成年哺乳动物组织干细胞的维持、自我更新和分化。既存在依赖β-连环蛋白的 Wnt 途径，也存在不依赖β-连环蛋白的 Wnt 途径，两者都影响发育中和成年组织中的干细胞命运。在这篇综述中，我们讨论了胚胎干细胞和人类中 Wnt 信号激活的反应，以及间充质、造血、肠、胃、表皮、乳腺和神经谱系的成体干细胞，并讨论了这些细胞类型中 Wnt 信号的必要性。由于 Wnt 信号在发育和维持过程中的重要作用，该途径的失调可能导致广泛的发育和遗传疾病，包括癌症。还讨论了 Wnt 信号如何为肿瘤提供养分并维持癌症干细胞的方式。因此，体内和体外操纵 Wnt 信号具有用于治疗方法的潜力，例如组织工程再生医学和抗癌治疗。尽管关于 Wnt 信号的完整细胞特异性反应以及与 BMP、Hedgehog 和 Notch 等途径的相互作用，仍有许多问题有待解决，但我们在此提供了关于 Wnt 信号及其对人类干细胞命运的控制的当前知识概述。
