Cell Stem Cell:潘氏细胞形成依赖白细胞介素-22

2022-09-15 科技部 科技部

研究结果表明,IL-22并不直接促进干细胞的再生能力,而是促进了潘氏细胞的产生,以及所有细胞类型中肠道抗菌肽的表达。

目前,白细胞介素-22(IL-22)被认为能够促进干细胞功能。潘氏细胞在以往的人类小肠类器官模型中并不存在。荷兰马克西玛公主儿科肿瘤中心研究团队通过优化人类小肠类器官模型揭示了潘氏细胞形成对IL-22的依赖性。该研究成果于近日发表在《Cell Stem Cell》上,题为:Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation。

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研究人员优化了人类小肠类器官(hSIO)的培养。在保持干细胞活跃的同时,能够分化为所有的细胞类型,包括成熟的潘氏细胞。研究发现,IL-22不会促进干细胞的扩增,而是延缓hSIO的生长。潘氏细胞是肠道抗菌肽的主要生产者。在hSIO中,IL-22是形成潘氏细胞的必要条件。引入与IL-22共受体的基因将导致hSIO中的潘氏细胞消失。此外,IL-22可以诱导宿主防御基因在肠细胞、吞咽细胞、潘氏细胞、肠道簇细胞及干细胞中的表达。

IL-22 regulates cellular diversity of hSIOs(A) UMAP of maturation medium (+IL-22)-cultured organoids for 14 days from scRNA-seq analysis (n = 1,283 cells). Descriptive cluster labels are shown. ISC, intestinal stem cell; TA1, transit-amplifying cell stage 1; TA2, transit-amplifying cell stage 2; EC, enterocyte; EEC, enteroendocrine cell.(B) Dot plot showing the relative expression and the percentage of cells expressing selected markers across scRNA-seq clusters. Two representative markers for each cluster are plotted.(C) Bar plot showing the relative Log2 fold change of cell populations in maturation medium-cultured organoids with or without the addition of IL-22.(D) MA plot showing differentially expressed genes between maturation medium-cultured organoids with or without the addition of IL-22 by pseudobulk analysis of scRNA-seq. Representative marker genes for the different cell types are color-coded as in (C). See also Figures S3 and S4 and Tables S2 and S3.

研究结果表明,IL-22并不直接促进干细胞的再生能力,而是促进了潘氏细胞的产生,以及所有细胞类型中肠道抗菌肽的表达。

论文链接:

Gui-Wei He, Lin Lin, Jeff DeMartino, Xuan Zheng, Nadzeya Staliarova, Talya Dayton, Harry Begthel, Willine J. van de Wetering, Eduard Bodewes, Jeroen van Zon, Sander Tans, Carmen Lopez-Iglesias, Peter J. Peters, Wei Wu, Daniel Kotlarz, Christoph Klein, Thanasis Margaritis, Frank Holstege, Hans Clevers. Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formationCell Stem Cell, 2022; DOI: 10.1016/j.stem.2022.08.002

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    2022-09-15 ms9000000862798697

    感谢大家的授课,收益菲薄

    0

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    2022-09-15 xulv123

    认真学习~~

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