肠类器官和肠样作为优秀的模型被小型化和简化,用于研究肠道生理和病理功能,药物筛选,和再生医学。最近,类器官和类肠在器官发育和营养代谢中的应用需求,免疫和癌症研究增加。但是对两者的比较研究很少,尤其是在免疫和新陈代谢方面,这也有利于进一步阐明隐窝干细胞和基质细胞的作用。在我们的研究中,通过组织培养从胎牛空肠获得“天然”类器官,并在不补充外源因子和基质胶的情况下从类器官中成功分离和培养了类肠。通过免疫组织化学和透射电子显微镜,这些微型肠道显示出与肠道相似的特征。基于转录组系统地比较了类器官和类肠。并通过qRT-PCR对部分结果进行了验证。我们的结果显示了KDGs(关键驱动基因)(例如,SLC13A1,HOXA7,HOXA6,HOXA5和HOXD4)富含与器官发育,形态和代谢相关的信号通路。KDG(例如,IL-6,PTGS2,CDH1,JUN,和EGFR)的肠样蛋白与癌症有关,MAPK,和免疫相关的信号通路。Wnt信号通路,在类器官中高度表达的基因,包括RSPO2,NOTUM,WNT6和RSPO3支持隐窝干细胞的稳态。肠样物质高表达CTNNB1和WNTs。此外,我们发现,由于细胞组成的不同,类器官和类肠在免疫和代谢方面具有不同的功能。因此,它表明类器官更兼容和全面,和肠样有资格研究免疫和癌症。
Intestinal organoids and enteroids as excellent models are miniaturized and simplified for studying intestinal physiological and pathological functions, drug screening, and regenerative medicine. Recently, the application demands for organoids and enteroids in organ development and nutrition metabolism, immune and cancer research increased. But there are few comparative studies on both of them, especially in immunity and metabolism, which is also conducive to further clarifying the role of crypt stem cells and stromal cells. In our study, \"natural\" organoids were obtained by tissue culture from fetal bovine jejunum and enteroids were successfully isolated and cultured from organoids without supplementing exogenous factors and Matrigel. These mini-guts displayed similar features to the intestine through immunohistochemistry and transmission electron microscopy. Organoid and enteroid were systematically compared based on the transcriptome. And some of the results were verified by qRT-PCR. Our results showed KDGs (Key driver genes) (e.g., SLC13A1, HOXA7, HOXA6, HOXA5, and HOXD4) of organoids enriched in signaling pathways related to organ development and morphology and metabolism. KDGs (e.g., IL-6, PTGS2, CDH1, JUN, and EGFR) of enteroid were involved in cancer, MAPK, and immune-related signaling pathways. To the Wnt signaling pathway, highly expressed genes in organoids, including RSPO2, NOTUM, WNT6, and RSPO3, supported the homeostasis of crypt stem cells. Enteroids highly expressed CTNNB1 and WNTs. In addition, we found that organoids and enteroids carried out different functions in immunity and metabolism due to different cell compositions. Therefore, it suggested organoid is more compatible and comprehensive, and enteroid is qualified for the research of immunity and cancer.