...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Oncogene >Utility of a bacterial infection model to study epithelial–mesenchymal transition, mesenchymal–epithelial transition or tumorigenesis
【24h】

Utility of a bacterial infection model to study epithelial–mesenchymal transition, mesenchymal–epithelial transition or tumorigenesis

机译：利用细菌感染模型研究上皮-间质转化，间质-上皮转化或肿瘤发生

获取原文
   

获取外文期刊封面封底 >>

       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

DCLK1 and Lgr5 have recently been identified as markers of quiescent and cycling stem cells in the small intestinal crypts, respectively. Epithelial鈥搈esenchymal transition (EMT) is a key development program that is often activated during cancer invasion and metastasis, and also imparts a self-renewal capability to disseminating cancer cells. Utilizing the Citrobacter rodentium (CR)-induced transmissible murine colonic hyperplasia (TMCH) model, we observed a relative decrease in DCLK1 expression in the colonic crypts, with significant shift towards stromal staining at peak (12 days post infection) hyperplasia, whereas staining for Lgr5 and Msi-1 increased several fold. When hyperplasia was regressing (days 20鈥?4), an expansion of DCLK1+ve cells in the CR-infected crypts compared with that seen in uninfected control was recorded. Purified colonic crypt cells exhibiting epigenetic modulation of the transforming growth factor-尾 (TGF尾), Wnt and Notch pathways on 12 or 34 days post infection formed monolayers in vitro , and underwent trans -differentiation into fibroblast-like cells that stained positive for vimentin, fibronectin and DCLK1. These cells when trypsinized and regrown in soft agar, formed colonospheres/organoids that developed into crypt-like structures (colonoids) in Matrigel and stained positive for DCLK1. Mice exhibiting 12 or 34 days of TMCH were given azoxymethane once for 8鈥塰 (Gp1) or weekly for 3 weeks (Gp2), and subjected to crypt isolation. Crypt cells from Gp1 animals formed monolayers as well as colonospheres in soft agar and nodules/tumors in nude mice. Crypt cells isolated from Gp2 animals failed to form the monolayers, but developed into colonospheres in soft agar and nodules/tumors in nude mice. Thus, both hyperplasia and increased presence of DCLK1+ve cells promote cellular transformation in response to a second hit. The TMCH model, therefore, provides an excellent template to study how alterations in intestinal stem cells promote trans -differentiation, crypt regeneration or colon carcinogenesis following bacterial infection.
机译：最近，DCLK1和Lgr5分别被鉴定为小肠隐窝中静态和循环干细胞的标志物。上皮-间充质转变（EMT）是一个关键的开发程序，通常在癌症侵袭和转移过程中被激活，并赋予其自我更新的能力以扩散癌细胞。利用柠檬酸杆菌（CR）诱导的可传播鼠结肠增生（TMCH）模型，我们观察到结肠隐窝中DCLK1表达的相对减少，在增生高峰期（感染后12天）明显向基质染色转移，而Lgr5和Msi-1的染色增加了几倍。当增生逐渐消退时（第20-4天），与未感染的对照相比，记录了CR感染的隐窝中DCLK1 + ve细胞的扩增。纯化的结肠隐窝细胞在感染后12或34天表现出表观遗传学的转化生长因子-β（TGFβ），Wnt和Notch途径的表观遗传调控，在体外形成单层，并进行转分化为成纤维细胞样波形蛋白，纤连蛋白和DCLK1染色呈阳性的细胞。这些细胞经过胰蛋白酶消化后在软琼脂中重新生长，形成了结肠球/类器官，并在基质胶中发展成隐窝状结构（类结肠），并对DCLK1染色呈阳性。对表现出TMCH 12或34天的小鼠，给予甲氧甲烷一次，每次8'（Gp1），或每周一次，持续3周（Gp2），并进行隐窝分离。来自Gp1动物的地穴细胞在软琼脂中形成单层以及结肠球，在裸鼠中形成结节/肿瘤。从Gp2动物中分离出的地穴细胞未能形成单层，但在软琼脂中发育成结肠球，在裸鼠中发育成结节/肿瘤。因此，增生和增加的DCLK1 + ve细胞的存在都促进了细胞对第二次命中的转化。因此，TMCH模型为研究肠道干细胞的变化如何在细菌感染后如何促进反式分化，隐窝再生或结肠癌发生提供了极好的模板。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号