在WNT介导的肠表皮质转化过程中,对流体Pdgfra表达细胞进行动态重编程
O Pellon-Cardenas1, P Rout1, S Hassan2
1Department of Genetics, Rutgers University, Piscataway, NJ, USA.
bioRxiv : the preprint server for biology
|February 3, 2025
概括
激活的PDGFRA+纤维细胞在早期WNT驱动的癌症中促进肠道再生. 肠道粘膜中的这种再生状态先于并有助于瘤形成.
科学领域:
- 胃肠病学 胃肠病学
- 在瘤学瘤学.
- 发展生物学 发展生物学
背景情况:
- 流体纤维细胞对于肠道平衡和干细胞支持至关重要.
- 沿着肠道密码 - 维卢斯轴的信号梯度是由纤维细胞调节的.
研究的目的:
- 调查PDGFRA表达纤维细胞在WNT介导的肠道瘤发生中的作用.
- 在早期癌症发育期间,识别参与纤维细胞-上皮层相互作用的信号通路.
主要方法:
- 在WNT驱动瘤发生的小鼠模型中,单细胞RNA测序 (RNA-seq) 的介质细胞.
- 功能性测试用于评估细胞间通信介质.
- 在β-catenin突变小鼠模型中进行基因操纵 (减少CDX2).
主要成果:
- 在WNT驱动的瘤发生过程中,PDGFRA+纤维细胞经历动态重编程.
- 这些纤维细胞分泌着连接体,诱导肠道粘膜中类似再生的状态.
- 在PDGFRA+纤维细胞中诱导TGFB信号传递,对于再生性有机体生长至关重要.
- 基因降低CDX2加速了WNT依赖的瘤转化.
结论:
- 在WNT驱动的瘤发生过程中,PDGFRA+纤维细胞被激活.
- 激活的纤维细胞促进表皮的再生状态,促进瘤的形成.
- 针对纤维细胞介导信号可能为肠癌提供治疗策略.
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