Fig. 7

Summary of main deregulated genes suggesting a dedifferentiation. Several of the main key Transcription Factors genes (Twist, Snail, ZEB) involved in EMT are upregulated in jou-overexpression. Consequently, several of their known targets as N-cadherin, Fibronectin, few Claudin and several KLF are upregulated. In parallel several genes are downregulated, as E-cadherin (CDH1), Claudin, α-catenin, β-catenin, several Annexin, several Keratin and several Myosin, as well as Protocadherin1-β13, αC1, γ9. Inversely, in the jou-depleted cells by siRNA, we rather observe the opposite phenotype, suggesting a MET (Mesenchymal-Epithelial-Transition). More particularly, we observe a decrease of two Transcription Factors as SOX4 and SOX8, although these two last have not yet been clearly demonstrated to induce MET. Several other genes (putatively their targets) are upregulated, while two key genes, as EPCAM and CD44 are downregulated. This last group of four genes (blue ellipse) could also suggests a CSC phenotype. Nevertheless, although we do not observe all the characteristic cells markers of the EMT, several of the deregulated genes in jou-overexpression strongly suggest an EMT, or at least a partial or hybrid EMT, as suggested by Pastushenko and Blanpain (2019) [19], while inversely, the knock-down of jouvence rather seems to direct the cells toward a MET