McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.
McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Stem Cell Reports. 2017 Sep 12;9(3):897-912. doi: 10.1016/j.stemcr.2017.07.024. Epub 2017 Aug 31.
Intestinal organoids derived from human pluripotent stem cells (hPSCs) are valuable in vitro research models that enable simplified access to human gastrointestinal tissues. Here, we report the in vitro generation of enterospheres (hEnS) from hPSC-derived gastrointestinal epithelial precursors. hEnS are cystic spheroids with a simple uniform structure composed entirely of intestinal epithelium. hEnS express markers of mature brush border cells and share a transcriptome profile similar to that of more mature intestinal organoids. Modulation of signaling cues enables control of hEnS growth and differentiation, including long-term propagation. We show that hEnS can be exploited for functional studies: hEnS display an innate immune response when treated with enteric pathogens, and transgenic modification of hEnS with a fluorescence cell-cycle reporter enables hEnS-forming stem cell enrichment. Our work establishes hEnS as an accessible and tractable in vitro modeling system for studying human gastrointestinal biology.
源自人类多能干细胞（hPSCs）的肠类器官是有价值的体外研究模型，可简化对人类胃肠道组织的研究。在此，我们报告了源自 hPSC 衍生的胃肠道上皮前体的肠类球体（hEnS）的体外生成。hEnS 是囊性球体，具有简单均匀的结构，完全由肠上皮组成。hEnS 表达成熟刷状缘细胞的标志物，其转录组谱与更成熟的肠类器官相似。信号通路的调节可控制 hEnS 的生长和分化，包括长期增殖。我们表明，hEnS 可用于功能研究：当用肠道病原体处理时，hEnS 会表现出先天免疫反应，并且用荧光细胞周期报告基因对 hEnS 进行转基因修饰可实现 hEnS 形成干细胞的富集。我们的工作确立了 hEnS 作为一种易于获取和处理的体外建模系统，可用于研究人类胃肠道生物学。
