Gasnier Maxime, Lim Hui Yi Grace, Barker Nick
A*STAR Institute of Molecular and Cell Biology, Singapore, Singapore.
A*STAR Institute of Molecular and Cell Biology, Singapore, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Curr Top Dev Biol. 2023;153:281-326. doi: 10.1016/bs.ctdb.2023.01.001. Epub 2023 Feb 1.
The intestinal epithelium plays a key role in digestion and protection against external pathogens. This tissue presents a high cellular turnover with the epithelium being completely renewed every 5days, driven by intestinal stem cells (ISCs) residing in the crypt bases. To sustain this dynamic renewal of the intestinal epithelium, the maintenance, proliferation, and differentiation of ISCs must be precisely controlled. One of the central pathways supporting ISC maintenance and dynamics is the Wnt pathway. In this chapter, we examine the role of Wnt signaling in intestinal epithelial homeostasis and tissue regeneration, including mechanisms regulating ISC identity and fine-tuning of Wnt pathway activation. We extensively discuss the contribution of the stem cell niche in maintaining Wnt signaling in the intestinal crypts that support ISC functions. The integration of these findings highlights the complex interplay of multiple niche signals and cellular components sustaining ISC behavior and maintenance, which together supports the immense plasticity of the intestinal epithelium.
肠上皮在消化和抵御外部病原体方面发挥着关键作用。该组织呈现出高细胞更新率,上皮细胞每5天完全更新一次,这是由位于隐窝底部的肠道干细胞(ISC)驱动的。为了维持肠上皮的这种动态更新,ISC的维持、增殖和分化必须得到精确控制。支持ISC维持和动态变化的核心途径之一是Wnt途径。在本章中,我们研究Wnt信号在肠上皮内稳态和组织再生中的作用,包括调节ISC特性的机制以及Wnt途径激活的微调。我们广泛讨论了干细胞微环境在维持支持ISC功能的肠隐窝中Wnt信号方面的作用。这些研究结果的整合突出了多种微环境信号和细胞成分之间复杂的相互作用,这些相互作用维持了ISC的行为和维持,共同支持了肠上皮的巨大可塑性。