The intestinal epithelium withstands continuous mechanical, chemical and biological insults despite its single-layered, simple epithelial structure. The crypt–villus tissue architecture in combination with rapid cell turnover enables the intestine to act both as a barrier and as the primary site of nutrient uptake. Constant tissue replenishment is fuelled by continuously dividing stem cells that reside at the bottom of crypts. These cells are nurtured and protected by specialized epithelial and mesenchymal cells, and together constitute the intestinal stem cell niche. Intestinal stem cells and early progenitor cells compete for limited niche space and, therefore, the ability to retain or regain stemness. Those cells unable to do so differentiate to one of six different mature cell types and move upwards towards the villus, where they are shed into the intestinal lumen after 3–5 days. In this Review, we discuss the signals, cell types and mechanisms that control homeostasis and regeneration in the intestinal epithelium. We investigate how the niche protects and instructs intestinal stem cells, which processes drive differentiation of mature cells and how imbalance in key signalling pathways can cause human disease.

尽管肠上皮具有单层，简单的上皮结构，但仍可承受连续的机械，化学和生物损伤。隐窝-绒毛组织结构与快速的细胞更新相结合，可使肠既充当屏障，又充当养分吸收的主要部位。通过不断分裂位于隐窝底部的干细胞，不断补充组织。这些细胞由专门的上皮细胞和间充质细胞培养和保护，并共同构成肠道干细胞的生态位。肠干细胞和早期祖细胞竞争有限的利基空间，因此保留或恢复干性的能力。那些无法做到这一点的细胞会分化为六种不同的成熟细胞类型之一，并向上移向绒毛，在3到5天后它们会掉入肠腔。在这篇综述中，我们讨论了控制肠上皮稳态和再生的信号，细胞类型和机制。我们调查利基如何保护和指导肠道干细胞，该过程驱动成熟细胞的分化，以及关键信号通路的失衡如何导致人类疾病。