CDX2-induced intestinal metaplasia in human gastric organoids derived from induced pluripotent stem cells

被引：16
|
作者：
Koide, Takahiro [1 ,2 ,3 ]
Koyanagi-Aoi, Michiyo [1 ,2 ,4 ]
Uehara, Keiichiro [1 ,2 ,5 ]
Kakeji, Yoshihiro [3 ]
Aoi, Takashi [1 ,2 ,4 ]
机构：
[1] Kobe Univ, Grad Sch Sci, Div Adv Med Sci, Technol & Innovat, Kobe, Hyogo, Japan
[2] Kobe Univ, Grad Sch Med, Dept iPS Cell Applicat, Kobe, Hyogo, Japan
[3] Kobe Univ, Grad Sch Med, Div Gastrointestinal Surg, Dept Surg, Kobe, Hyogo, Japan
[4] Kobe Univ Hosp, Ctr Human Resource Dev Regenerat Med, Kobe, Hyogo, Japan
[5] Kobe Univ, Grad Sch Med, Dept Diagnost Pathol, Kobe, Hyogo, Japan
来源：
ISCIENCE | 2022年 / 25卷 / 05期
关键词：
TRANSCRIPTION FACTORS; EPITHELIAL-CELLS; SOX2; EXPRESSION; IN-VITRO; STOMACH; CDX2; CANCER; ADENOCARCINOMAS; DIFFERENTIATION; REGENERATION;
D O I：
10.1016/j.isci.2022.104314
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：
07 ; 0710 ; 09 ;
摘要：
Intestinal metaplasia is related to gastric carcinogenesis. Previous studies have suggested the important role of CDX2 in intestinal metaplasia, and several reports have shown that the overexpression of CDX2 in mouse gastric mucosa caused intestinal metaplasia. However, no study has examined the induction of intestinal metaplasia using human gastric mucosa. In the present study, to produce an intestinal metaplasia model in human gastric mucosa in vitro, we differentiated human-induced pluripotent stemcells (hiPSC) to gastric organoids, followed by the overexpression of CDX2 using a tet-on system. The overexpression of CDX2 induced, although not completely, intestinal phenotypes and the enhanced expression of many, but not all, intestinal genes and previously reported intestinal metaplasia-related genes in the gastric organoids. This model can help clarify the mechanisms underlying intestinal metaplasia and carcinogenesis in human gastric mucosa and develop therapies to restitute precursor conditions of gastric cancer to normal mucosa.
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收藏
页数：19
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