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动态重编程PDGFRA表达的干细胞促进WNT驱动的转化,通过促进肠上皮质的胎儿状状态

Oscar Pellon-Cardenas¹, Prateeksha Rout², Sohaib Hassan³

¹Rutgers, The State University of New Jersey United States.

Cancer research

|March 5, 2026

概括

在WNT驱动的瘤发生过程中,PDGFRA+纤维细胞在肠上皮质中促进胎儿状的状态. 这种涉及TGFβ信号的重编程促进了早期瘤形成和组织转化.

科学领域:

胃肠病学胃肠病学
癌症生物学癌症生物学
发展生物学发展生物学

背景情况:

流体纤维细胞调节肠道干细胞和信号梯度.
表达PDGFRA的纤维细胞与早期WNT介导的瘤发生有关.

研究的目的:

调查PDGFRA+纤维细胞在WNT驱动的肠癌发生中的作用.
确定在瘤开始期间调解纤维细胞-上皮相互作用的信号通路.

主要方法:

单细胞RNA测序 (RNA-seq) 的小鼠肠道介质.
使用有机体和WNT驱动瘤发生的小鼠模型进行功能性测试.
在β-catenin突变肠上皮质中减少CDX2的分析.

主要成果:

在WNT瘤发生过程中,PDGFRA+纤维细胞重新编程到类似胎儿的状态.
在PDGFRA+纤维细胞中,TGFβ信号由致癌性表皮诱导,并维持胎儿类的有机体生长.
减少CDX2通过促进胎儿状的状态来加速WNT依赖的瘤发生.

结论:

在WNT驱动的肠道瘤发生过程中,PDGFRA+纤维细胞被激活.
这些激活的纤维细胞促进胎儿类的上皮状况,这在瘤形成之前并促进了瘤形成.
向纤维细胞激活和TGFβ信号可能为WNT驱动的肠瘤提供治疗策略.

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