文章基本信息

标题：CDX2-induced intestinal metaplasia in human gastric organoids derived from induced pluripotent stem cells
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作者：Takahiro Koide ; Michiyo Koyanagi-Aoi ; Keiichiro Uehara 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：5
页码：1-20
DOI：10.1016/j.isci.2022.104314
语种：English
出版社：Elsevier
摘要：SummaryIntestinal 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 mucosain vitro, we differentiated human-induced pluripotent stem cells (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.Graphical abstractDisplay OmittedHighlights•We established the drug-inducible CDX2 expression in gastric organoids from hiPSCs•Intestinal phenotypes were induced, although not completely, in the gastric organoids•Many, but not all, intestinal genes and metaplasia-related genes were upregulated•Endogenous CDX2—an intestinal master transcription factor—was not upregulatedBiological sciences; Cell biology; Stem cells research