Oncode Institute, Utrecht, Netherlands.
Hubrecht Institute, Utrecht, Netherlands.
Nat Rev Mol Cell Biol. 2021 Jan;22(1):39-53. doi: 10.1038/s41580-020-0278-0. Epub 2020 Sep 21.
Intestinal stem cells at the bottom of crypts fuel the rapid renewal of the different cell types that constitute a multitasking tissue. The intestinal epithelium facilitates selective uptake of nutrients while acting as a barrier for hostile luminal contents. Recent discoveries have revealed that the lineage plasticity of committed cells - combined with redundant sources of niche signals - enables the epithelium to efficiently repair tissue damage. New approaches such as single-cell transcriptomics and the use of organoid models have led to the identification of the signals that guide fate specification of stem cell progeny into the six intestinal cell lineages. These cell types display context-dependent functionality and can adapt to different requirements over their lifetime, as dictated by their microenvironment. These new insights into stem cell regulation and fate specification could aid the development of therapies that exploit the regenerative capacity and functionality of the gut.
肠干细胞位于隐窝底部，为构成多功能组织的不同细胞类型的快速更新提供动力。肠上皮细胞促进了营养物质的选择性吸收，同时也充当了抵御腔内容物的屏障。最近的发现表明，定向细胞的谱系可塑性——结合多余的龛位信号源——使上皮细胞能够有效地修复组织损伤。单细胞转录组学和类器官模型等新方法的应用，导致了指导干细胞后代向六个肠细胞谱系命运特化的信号的鉴定。这些细胞类型表现出与上下文相关的功能，并可以根据其微环境，在其整个生命周期内适应不同的需求。这些关于干细胞调控和命运特化的新见解可能有助于开发利用肠道再生能力和功能的治疗方法。
