{"title":"上皮细胞分泌的细胞外基质生态位驱动肠道类器官的形成","authors":"Antonius Chrisnandy, Matthias P. Lutolf","doi":"10.1016/j.devcel.2025.06.026","DOIUrl":null,"url":null,"abstract":"Intestinal organoids have become an important model system in basic and translational research, but their culture typically relies on an ill-defined laminin-rich extracellular matrix (ECM). Using tunable and chemically defined 3D hydrogels, we systematically explored the role of the ECM during murine and human intestinal organoid development. We discovered that without exogenous laminin, stem cells developed into intestinal epithelia with a large proportion of regenerative cells. This population secreted a laminin-rich basement membrane that functioned as a <em>de novo</em> stem cell niche, promoting organoid formation independent of exogenous laminin. We identified ubiquitous expression of laminin chains Lama3, Lamb3, and Lamc2, but Lamb1 and Lamc1 were spatially restricted to the crypt domain. Epithelial-cell-secreted basement membranes extracted from organoids promoted the formation of patterned organoids. Our results highlight the utility of chemically defined matrices for studying ECM biology and pave the way for the replacement of animal-derived matrices in organoid culture.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"12 1","pages":""},"PeriodicalIF":10.7000,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"An extracellular matrix niche secreted by epithelial cells drives intestinal organoid formation\",\"authors\":\"Antonius Chrisnandy, Matthias P. Lutolf\",\"doi\":\"10.1016/j.devcel.2025.06.026\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Intestinal organoids have become an important model system in basic and translational research, but their culture typically relies on an ill-defined laminin-rich extracellular matrix (ECM). Using tunable and chemically defined 3D hydrogels, we systematically explored the role of the ECM during murine and human intestinal organoid development. We discovered that without exogenous laminin, stem cells developed into intestinal epithelia with a large proportion of regenerative cells. This population secreted a laminin-rich basement membrane that functioned as a <em>de novo</em> stem cell niche, promoting organoid formation independent of exogenous laminin. We identified ubiquitous expression of laminin chains Lama3, Lamb3, and Lamc2, but Lamb1 and Lamc1 were spatially restricted to the crypt domain. Epithelial-cell-secreted basement membranes extracted from organoids promoted the formation of patterned organoids. Our results highlight the utility of chemically defined matrices for studying ECM biology and pave the way for the replacement of animal-derived matrices in organoid culture.\",\"PeriodicalId\":11157,\"journal\":{\"name\":\"Developmental cell\",\"volume\":\"12 1\",\"pages\":\"\"},\"PeriodicalIF\":10.7000,\"publicationDate\":\"2025-07-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Developmental cell\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.devcel.2025.06.026\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Developmental cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.devcel.2025.06.026","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
An extracellular matrix niche secreted by epithelial cells drives intestinal organoid formation
Intestinal organoids have become an important model system in basic and translational research, but their culture typically relies on an ill-defined laminin-rich extracellular matrix (ECM). Using tunable and chemically defined 3D hydrogels, we systematically explored the role of the ECM during murine and human intestinal organoid development. We discovered that without exogenous laminin, stem cells developed into intestinal epithelia with a large proportion of regenerative cells. This population secreted a laminin-rich basement membrane that functioned as a de novo stem cell niche, promoting organoid formation independent of exogenous laminin. We identified ubiquitous expression of laminin chains Lama3, Lamb3, and Lamc2, but Lamb1 and Lamc1 were spatially restricted to the crypt domain. Epithelial-cell-secreted basement membranes extracted from organoids promoted the formation of patterned organoids. Our results highlight the utility of chemically defined matrices for studying ECM biology and pave the way for the replacement of animal-derived matrices in organoid culture.
期刊介绍:
Developmental Cell, established in 2001, is a comprehensive journal that explores a wide range of topics in cell and developmental biology. Our publication encompasses work across various disciplines within biology, with a particular emphasis on investigating the intersections between cell biology, developmental biology, and other related fields. Our primary objective is to present research conducted through a cell biological perspective, addressing the essential mechanisms governing cell function, cellular interactions, and responses to the environment. Moreover, we focus on understanding the collective behavior of cells, culminating in the formation of tissues, organs, and whole organisms, while also investigating the consequences of any malfunctions in these intricate processes.