Leucine-rich repeat-containing G-protein coupled receptor 5 enriched organoids under chemically-defined growth conditions.

Autor: Hahn S; Department of Microbiology and CHA Organoid Research Center, School of Medicine, CHA University, South Korea., Kim MS; Department of Radiation Oncology, Bundang CHA Medical Center, South Korea., Choi SY; Department of Microbiology and CHA Organoid Research Center, School of Medicine, CHA University, South Korea., Jeong S; Department of Microbiology and CHA Organoid Research Center, School of Medicine, CHA University, South Korea., Jee J; Department of Microbiology and CHA Organoid Research Center, School of Medicine, CHA University, South Korea., Kim HK; Department of Microbiology and CHA Organoid Research Center, School of Medicine, CHA University, South Korea., Jeong SY; Department of Microbiology and CHA Organoid Research Center, School of Medicine, CHA University, South Korea., Shin H; Department of Radiation Oncology, Bundang CHA Medical Center, South Korea., Kim HS; Pancreatobiliary Cancer Clinic, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, South Korea., Park JS; Pancreatobiliary Cancer Clinic, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, South Korea; Department of Surgery, Gangnam Severance Hospital, South Korea., Yoo J; Department of Microbiology and CHA Organoid Research Center, School of Medicine, CHA University, South Korea. Electronic address: jongmanyoo@cha.ac.kr.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2019 Jan 08; Vol. 508 (2), pp. 430-439. Date of Electronic Publication: 2018 Nov 28.
DOI: 10.1016/j.bbrc.2018.11.003
Abstrakt: An organoid is a complex, multi-cell three-dimensional (3D) structure that contains tissue-specific cells. Epithelial stem cells, which are marked by leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), have the potential for self-renewal and expansion as organoids. However, in the case of intestinal organoids from Lgr5-EGFP-IRES-CreERT2 transgenic mice, in vitro expansion of the Lgr5 expression is limited in a culture condition supplemented with essential proteins, such as epidermal growth factor (E), noggin (N), and R-spondin 1 (R). In this study, we hypothesized that self-renewal of Lgr5+ stem cells in a 3D culture system can be stimulated by defined compounds (CHIR99021, Valproic acid, Y-27632, and A83-01). Our results demonstrated that dissociated single cells from organoids were organized into a 3D structure in the four compounds containing the ENR culture medium in a 3D and two-dimensional (2D) culture system. Moreover, the Lgr5 expression level of organoids from the ENR- and compound-containing media increased. Furthermore, the conversion of cultured Lgr5+ stem cells from 2D to 3D was confirmed. Therefore, defined compounds promote the expansion of Lgr5+ stem cells in organoids.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE