Intestinal Morphogenesis in Development, Regeneration, and Disease: The Potential Utility of Intestinal Organoids for Studying Compartmentalization of the Crypt-Villus Structure.
Intestinal Morphogenesis in Development, Regeneration, and Disease: The Potential Utility of Intestinal Organoids for Studying Compartmentalization of the Crypt-Villus Structure.
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DOI：
10.3389/fcell.2020.593969
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发表时间：
2020
影响因子：
5.5
通讯作者：
Son MY
中科院分区：
文献类型：
--
作者：
Kwon O;Han TS;Son MY
在发育、组织再生和疾病进展过程中，肠上皮的形态和结构是动态重排的。肠上皮形态发生的最重要特征是隐窝-绒毛单位的重复分隔结构，这对维持肠道的动态平衡和功能至关重要。已知异常结构与疾病的发展和进展密切相关。因此，了解肠腺绒毛结构是如何形成和生长的，对于阐明肠上皮的生理和病理生理作用是至关重要的。然而，在使用动物模型时，由于明显的物种间差异和实时监测的困难，在理解隐窝-绒毛轴的划分方面仍然存在关键的知识差距。最近，诸如器官培养、谱系追踪和单细胞测序等新兴技术使得对肠上皮形态发生的内在机制的评估成为可能。在这篇综述中，我们讨论了在肠上皮隐窝绒毛结构的形成、维持和再生中起核心作用的调节因子和信号通路的最新研究。此外，我们还讨论了这些因子和途径如何在发育、组织再生和疾病中发挥作用。我们进一步探索目前的三维肠道器官技术如何有助于理解隐窝-绒毛的区隔，重点介绍与自组织过程驱动的隐窝-绒毛结构的启动和繁殖相关的新发现。我们还讨论了以隐窝绒毛结构异常为特征的肠道疾病，为开发针对肠道形态发生和隐窝绒毛形成的新的治疗策略提供了见解。
The morphology and structure of the intestinal epithelium are rearranged dynamically during development, tissue regeneration, and disease progression. The most important characteristic of intestinal epithelial morphogenesis is the repetitive compartmentalized structures of crypt-villus units, which are crucial for maintaining intestinal homeostasis and functions. Abnormal structures are known to be closely associated with disease development and progression. Therefore, understanding how intestinal crypt-villus structures are formed and grown is essential for elucidating the physiological and pathophysiological roles of the intestinal epithelium. However, a critical knowledge gap in understanding the compartmentalization of the crypt-villus axis remains when using animal models, due to obvious inter-species differences and difficulty in real-time monitoring. Recently, emerging technologies such as organoid culture, lineage tracing, and single cell sequencing have enabled the assessment of the intrinsic mechanisms of intestinal epithelial morphogenesis. In this review, we discuss the latest research on the regulatory factors and signaling pathways that play a central role in the formation, maintenance, and regeneration of crypt-villus structures in the intestinal epithelium. Furthermore, we discuss how these factors and pathways play a role in development, tissue regeneration, and disease. We further explore how the current technology of three-dimensional intestinal organoids has contributed to the understanding of crypt-villus compartmentalization, highlighting new findings related to the self-organizing-process-driven initiation and propagation of crypt-villus structures. We also discuss intestinal diseases featuring abnormalities of the crypt-villus structure to provide insights for the development of novel therapeutic strategies targeting intestinal morphogenesis and crypt-villus formation.