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Research progress on Lgr5-mediated stem cell regulation and digestive system organoid formation
- Synthetic Biology Journal Vol. 7, Issue 1, Pages: 233-245(2026)
- 作者机构：
1.湖南师范大学生命科学学院， 动物肠道功能调控湖南省重点实验室， 湖南省动物肠道生态与健康国际联合实验室，湖南 长沙 410081
2.中国科学院动物研究所交叉科学中心， 北京 100101
3.中国科学院亚热带农业生态研究所，动物营养生理与代谢过程湖南省重点实验室，畜禽养殖污染控制与资源化技术国家工程实验室，湖南 长沙 410125
- 作者简介：
- 基金信息：
DOI：10.12211/2096-8280.2025-098
CLC： Q813Received：12 November 2025，
Revised：2026-01-14，
Published：28 February 2026
- 稿件说明：
移动端阅览
姚拓新， 李幸， 印遇龙， 何流琴. Lgr5介导的干细胞调控与消化系统类器官形成的研究进展［J］. 合成生物学， 2026， 7（1）： 233-245
YAO Tuoxin， LI Xing， YIN Yulong， HE Liuqin. Research progress on Lgr5-mediated stem cell regulation and digestive system organoid formation［J］. Synthetic Biology Journal， 2026， 7（1）： 233-245
姚拓新， 李幸， 印遇龙， 何流琴. Lgr5介导的干细胞调控与消化系统类器官形成的研究进展［J］. 合成生物学， 2026， 7（1）： 233-245 DOI： 10.12211/2096-8280.2025-098.
YAO Tuoxin， LI Xing， YIN Yulong， HE Liuqin. Research progress on Lgr5-mediated stem cell regulation and digestive system organoid formation［J］. Synthetic Biology Journal， 2026， 7（1）： 233-245 DOI： 10.12211/2096-8280.2025-098.
摘要
作为干细胞特异性标志物的富含亮氨酸重复序列的G蛋白偶联受体5（leucine-rich repeat-containing G protein-coupled receptor 5，Lgr5）是细胞膜上的一段七次跨膜受体蛋白，它通过调控Wnt/β-catenin信号维持干细胞增殖与分化平衡，同时与BMP、Notch等通路耦合，协同促进类器官的形成。类器官是一种在体外培养的、具有类似真实器官结构和功能的3D细胞团，不仅能还原组织复杂的结构，也能模拟组织的生理环境，是各种组织器官研究比较精准的体外模型。近年来，类器官为营养吸收、疾病建模、药物筛选和基因编辑等方面的研究提供了比细胞更真实的模型，在生物医学领域引起了广泛关注。因此，本文重点综述了Lgr5通过与R-spondins结合并增强Wnt/β-catenin信号通路，进而调控干细胞自更新与定向分化的分子机制，阐述了其作为核心驱动力在构建微型肠道、肝脏及胰腺类器官中的关键作用，同时，详细探讨了消化道类器官在模拟结直肠癌、非酒精性脂肪肝等疾病病理，以及作为供体组织用于肠黏膜损伤修复和胆管重建等再生医学领域的具体应用，最后，针对目前类器官技术面临的基质胶成分不明确、缺乏血管化和免疫微环境等挑战，提出了结合微流控芯片、合成生物支架及多细胞共培养技术实现类器官复杂化、标准化的未来发展方向，旨在为消化系统疾病的精准治疗提供理论依据。
Abstract
Leucine-rich repeat-co
ntaining G protein-coupled receptor 5 (Lgr5) has been identified as a reliable marker for adult stem cells in various tissues. With a transmembrane region consisting of seven α-helical segments
Lgr5 plays a pivotal role in maintaining the delicate balance between stem cell self-renewal and differentiation. This regulatory function is primarily executed through the potentiation of the Wnt/β-catenin signaling pathway upon binding with its ligands
R-spondins. This article provides a comprehensive review on molecular mechanisms by which Lgr5 modulates stem cell behavior and its indispensable role in the formation of digestive system organoids
including intestine
liver
and pancreas. We first elucidate the synergistic interplay between Lgr5-mediated Wnt signaling and other crucial pathways such as BMP
Notch
and EGF
which collectively create a biomimetic “niche” for organoid development
in vitro.
This Lgr5-mediated self-organization serves as the biological foundation for constructing three-dimensional (3D) organoids
as 3D cell clusters derive from stem cells with structural and functional characteristics that closely mimic native organs. Compared to traditional 2D cell cultures
organoids offer a superior model for studying tissue physiology and complex cell-cell interactions. Furthermore
this review highlights the diverse applications of digestive system organoids in biomedical research. In disease modeling
we discuss how these platforms simulate the pathological progression of colorectal cancer
non-alcoholic fatty liver disease
and hereditary metabolic disorders through CRISPR-Cas9 gene editing and environmental induction. In the field of regenerative medicine
the potential of organoids as transplantable units for repairing intestinal mucosal damage and reconstructing bile duct structures is explored. Despite the significant advancements
critical challenges remain in the current development of organoid technology. We identify several major limitations. First
organoids are highly depen
dent on animal-derived basement membrane matrix
which has poorly defined components. Second
current models lack functional vascularization. Third
they lack an integrated immune microenvironment. These limitations restrict the translational potential of organoid technology. To address these challenges
we propose future research directions
emphasizing the integration of microfluidic “organ-on-a-chip” systems
synthetic bio-scaffolds
and multi-lineage co-culture techniques. These innovations aim for more complexity and standardization in organoid models
providing a more robust theoretical and technical foundation for personalized medicine and drug discovery for digestive diseases.
2
关键词
Keywords
references
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