小柯机器人

近日，英国剑桥大学Benjamin D. Simons、Bon-Kyoung Koo等研究人员合作实现对癌基因驱动的肠道干细胞微环境重塑的追踪。2021年6月2日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员展示了一种与癌基因相关的多色报告小鼠模型——Red2Onco系统，它能够对同一组织中的突变型和野生型细胞进行差异追踪。通过将该系统应用于小肠，研究人员表明表达癌基因的突变隐窝改变了邻近野生型隐窝的细胞组织，从而加速了克隆漂移。表达致癌KRAS或PI3K的隐窝分泌抑制局部干细胞活性的BMP配体，而由具有致癌PI3K的隐窝诱导的PDGFR^loCD81⁺基质细胞的变化改变了WNT信号传导环境。总之，这些结果揭示出致癌基因驱动的旁分泌重塑如何创造一个不利于野生型组织维持的微环境，进而促进由致癌克隆主导的转化。

据了解，肿瘤细胞与周围微环境之间的相互作用有助于肿瘤进展、转移和复发。尽管果蝇中的镶嵌分析提高了人们对此类相互作用的理解，但在脊椎动物中设计并行方法一直很困难。

附：英文原文

Title: Tracing oncogene-driven remodelling of the intestinal stem cell niche

Author: Min Kyu Yum, Seungmin Han, Juergen Fink, Szu-Hsien Sam Wu, Catherine Dabrowska, Teodora Trendafilova, Roxana Mustata, Lemonia Chatzeli, Roberta Azzarelli, Irina Pshenichnaya, Eunmin Lee, Frances England, Jong Kyoung Kim, Daniel E. Stange, Anna Philpott, Joo-Hyeon Lee, Bon-Kyoung Koo, Benjamin D. Simons

Issue&Volume: 2021-06-02

Abstract: Interactions between tumour cells and the surrounding microenvironment contribute to tumour progression, metastasis and recurrence1,2,3. Although mosaic analyses in Drosophila have advanced our understanding of such interactions4,5, it has been difficult to engineer parallel approaches in vertebrates. Here we present an oncogene-associated, multicolour reporter mouse model—the Red2Onco system—that allows differential tracing of mutant and wild-type cells in the same tissue. By applying this system to the small intestine, we show that oncogene-expressing mutant crypts alter the cellular organization of neighbouring wild-type crypts, thereby driving accelerated clonal drift. Crypts that express oncogenic KRAS or PI3K secrete BMP ligands that suppress local stem cell activity, while changes in PDGFRloCD81+ stromal cells induced by crypts with oncogenic PI3K alter the WNT signalling environment. Together, these results show how oncogene-driven paracrine remodelling creates a niche environment that is detrimental to the maintenance of wild-type tissue, promoting field transformation dominated by oncogenic clones.

DOI: 10.1038/s41586-021-03605-0

Source: https://www.nature.com/articles/s41586-021-03605-0

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html