Growing Self-Organizing Mini-Guts from a Single Intestinal Stem Cell: Mechanism and Applications

被引:950
作者
Sato, Toshiro [1 ]
Clevers, Hans [2 ,3 ]
机构
[1] Keio Univ, Sch Med, Dept Gastroenterol, Tokyo 1608582, Japan
[2] Koninklijke Nederlandse Akad Wetenschappen, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands
[3] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands
关键词
IN-VITRO; EXPRESSION MARKS; WNT RECEPTORS; DIFFERENTIATION; EPITHELIUM; EXPANSION; COLON; HOMEOSTASIS; POPULATION; INHIBITION;
D O I
10.1126/science.1234852
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Recent examples have highlighted how stem cells have the capability to initiate morphogenesis in vitro; that is, to generate complex structures in culture that closely parallel their in vivo counterparts. Lgr5, the receptor for the Wnt-agonistic R-spondins, marks stem cells in multiple adult organs of mice and humans. In R-spondin-based three-dimensional cultures, these Lgr5 stem cells can grow into ever-expanding epithelial organoids that retain their original organ identity. Single Lgr5 stem cells derived from the intestine can be cultured to build epithelial structures that retain hallmarks of the in vivo epithelium. Here, we review the mechanisms that support this notable example of self-organization and discuss applications of this technology for stem cell research, disease modeling (e. g., for colorectal cancer and cystic fibrosis), and regenerative medicine.
引用
收藏
页码:1190 / 1194
页数:5
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