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共生菌对肠道祖细胞黏附、分裂对称性和致瘤性的差异影响。

Differential effects of commensal bacteria on progenitor cell adhesion, division symmetry and tumorigenesis in the intestine.

机构信息

Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2E1, Canada.

Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2E1, Canada.

出版信息

Development. 2021 Mar 9;148(5):dev186106. doi: 10.1242/dev.186106.

Abstract

Microbial factors influence homeostatic and oncogenic growth in the intestinal epithelium. However, we know little about immediate effects of commensal bacteria on stem cell division programs. In this study, we examined the effects of commensal species on homeostatic and tumorigenic stem cell proliferation in the female intestine. We identified as a potent stimulator of stem cell divisions. In a wild-type midgut, activates growth regulatory pathways that drive stem cell divisions. In a Notch-deficient background, -mediated proliferation causes rapid expansion of mutant progenitors, leading to accumulation of large, multi-layered tumors throughout the midgut. Mechanistically, we showed that disrupts expression and subcellular distribution of progenitor cell integrins, supporting symmetric divisions that expand intestinal stem cell populations. Collectively, our data emphasize the impact of commensal microbes on division and maintenance of the intestinal progenitor compartment.

摘要

微生物因素影响肠道上皮细胞的稳态和致癌生长。然而,我们对共生细菌对干细胞分裂程序的直接影响知之甚少。在这项研究中,我们研究了共生细菌对雌性肠道中稳态和致瘤干细胞增殖的影响。我们发现 是干细胞分裂的有力刺激物。在野生型中肠中, 激活了驱动干细胞分裂的生长调节途径。在 Notch 缺陷背景下, -介导的增殖导致突变体祖细胞的快速扩张,导致整个中肠中积累大的、多层的肿瘤。从机制上讲,我们表明 破坏了祖细胞整联蛋白的表达和细胞内分布,支持扩大肠道干细胞群体的对称分裂。总的来说,我们的数据强调了共生微生物对肠道祖细胞区室的分裂和维持的影响。

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