Tsc1a knockdown and Mycobacterium marinum infection

We identify a putative link between miR-126 and the tsc1a signalling pathway resulting in the suppression of permissive macrophage accumulation at early zebrafish-M. marinum granulomas. Mechanistically, we find a detrimental effect of tsc1a expression that renders zebrafish embryos susceptible to higher bacterial burden and increased cell death via mTOR inhibition. Overall design: Whole zebrafish embryo RNAseq of scram and tsc1a gRNA/Cas9-injected, with and without Mycobacterium marinum infection

本研究证实miR-126（microRNA-126）与tsc1a信号通路之间存在潜在关联，该通路可抑制斑马鱼感染海分枝杆菌（Mycobacterium marinum）早期肉芽肿内的促定植巨噬细胞聚集。从机制层面来看，我们发现tsc1a的表达存在不利影响：该影响通过抑制mTOR（哺乳动物雷帕霉素靶蛋白，mammalian target of rapamycin）通路，使斑马鱼胚胎更易承受更高的细菌负荷，并加剧细胞死亡。整体实验设计：对注射了阴性对照sgRNA（scram gRNA）与tsc1a sgRNA/Cas9的斑马鱼胚胎，分别设置感染与未感染海分枝杆菌的条件开展全胚胎RNA测序。