Mehra Lalita, Bhowmik Subham, Makharia Govind K, Das Prasenjit
Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India.
Department of Gastroenterology and Human Nutritions, All India Institute of Medical Sciences, New Delhi, 110 029, India.
Indian J Gastroenterol. 2025 Feb;44(1):8-23. doi: 10.1007/s12664-024-01699-8. Epub 2024 Nov 8.
The intestinal stem cell (ISC) niche is vital for maintaining the integrity and function of the intestinal epithelium. ISC populations, characterized by their high proliferation and multipotency, reside within a specialized microenvironment at the base of crypts. Crypt base columnar (CBC) cells at the deepest part of crypts serve as replicating ISCs, while position 4 label-retaining cells (LRCs) located higher up in the crypts are also important for ISC maintenance during experiments. The interplay between CBCs, position 4 LRCs, transient amplifying (TA) cells and other niche components, including the pericrypt stromal cells, ensures a continuous supply of differentiated epithelial cells. Recent advancements in ISC biomarker studies have provided valuable insights into their molecular signatures, regulatory pathways and roles in the pathogenesis of intestinal disorders. Understanding the ISC niche has significant therapeutic implications, as manipulating ISC behaviors and regenerating damaged or diseased intestinal tissue show promise for novel therapeutic approaches. ISC organoids have also provided a platform for studying intestinal diseases and testing personalized therapies. This comprehensive review covers the anatomical composition, physiological regulation, ISC biomarker studies, contribution to intestinal disorder pathogenesis and potential therapeutic implications of the ISC niche.
肠道干细胞(ISC)生态位对于维持肠道上皮的完整性和功能至关重要。ISC群体以其高增殖能力和多能性为特征,存在于隐窝底部的特殊微环境中。隐窝最深处的隐窝基底柱状(CBC)细胞作为增殖的ISC,而位于隐窝较高位置的4号位置标记保留细胞(LRC)在实验期间对ISC的维持也很重要。CBC、4号位置LRC、短暂增殖(TA)细胞与其他生态位成分(包括隐窝周围基质细胞)之间的相互作用,确保了分化上皮细胞的持续供应。ISC生物标志物研究的最新进展为其分子特征、调控途径以及在肠道疾病发病机制中的作用提供了有价值的见解。了解ISC生态位具有重要的治疗意义,因为操纵ISC行为和再生受损或患病的肠道组织有望成为新的治疗方法。ISC类器官也为研究肠道疾病和测试个性化疗法提供了一个平台。这篇综述涵盖了ISC生态位的解剖组成、生理调节、ISC生物标志物研究、对肠道疾病发病机制的贡献以及潜在的治疗意义。