Effects of a small molecule R-spondin-1 substitute RS-246204 on a mouse intestinal organoid culture
PDF | HTML | Supplementary Files | How to cite
Metrics: PDF 2143 views | HTML 3308 views | ?
Myeong-Ok Nam1,2, Soojung Hahn1,2, Joo Hyun Jee1,2, Tae-Sun Hwang2,3, Ho Yoon2,3, Dong Hyeon Lee2,4, Min-Soo Kwon2,5 and Jongman Yoo1,2
1Department of Microbiology and School of Medicine, CHA University, Seongnam-si, Gyeonggi-do 13488, South Korea
2Institute of Basic Medical Sciences, School of Medicine, CHA University, Seongnam-si, Gyeonggi-do 13488, South Korea
3Department of Anatomy, School of Medicine, CHA University, Seongnam-si, Gyeonggi-do 13488, South Korea
4Department of Physiology, School of Medicine, CHA University, Seongnam-si, Gyeonggi-do 13488, South Korea
5Department of Pharmacology, School of Medicine, CHA University, Seongnam-si, Gyeonggi-do 13488, South Korea
Jongman Yoo, email: [email protected]
Keywords: intestinal organoid; enteroid; R-spondin-1; RS-246204: Lgr5
Received: September 26, 2017 Accepted: December 05, 2017 Published: December 26, 2017
Organoids, a multi-cellular and organ-like structure cultured in vitro, can be used in a variety of fields such as disease modeling, drug discovery, or cell therapy development. When organoids derived from Lgr5 stem cells are cultured ex vivo, recombinant R-spondin-1 protein should be added at a high concentration for the initiation and maintenance of the organoids. Because the addition of large amounts of R-spondin-1 greatly increases the cost of organoids, the organoids grown with R-spondin-1 are not practical for large-scale drug screening and for the development of therapeutic agents. In this study, we tried to find a R-spondin-1 substitute compound that is able initiate small intestinal organoids without the use of the R-spondin-1 protein; thus, using organoid media that each included one compound from among an 8,364 compound library instead of R-spondin-1, we observed whether organoids were established from the crypts of the small intestine. As a result, we found one compound that could promote the initial formation and growth of enteroids in the medium without R-spondin-1 and named it RS-246204. The enteroids grown with RS-246204 had a similar differentiation capacity as well as self-renewal capacity as the enteroids grown with R-spondin-1. Furthermore, the RS-246204-derived enteroids could successfully produce the forskolin induced swelling and the organoid based epithelial to mesenchymal transition model. This compound could be used for developing a cost-efficient culturing method for intestinal organoids as well as for exploring Lgr5 signaling, intestinal stem cell physiology and therapeutics for GI tract diseases.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.