Retinoic acid(RA)and 2-phospho-L-ascorbic acid trisodium salt(AscPNa)promote the reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells.In the current studies,the lower abilities of RA and AscP...Retinoic acid(RA)and 2-phospho-L-ascorbic acid trisodium salt(AscPNa)promote the reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells.In the current studies,the lower abilities of RA and AscPNa to promote reprogramming in the presence of each other suggested that they may share downstream pathways at least partially.The hypothesis was further supported by the RNA-seq analysis which demonstrated a high-level overlap between RA-activated and AscPNa activated genes during reprogramming.In addition,RA upregulated Glut1/3,facilitated the membrane transportation of dehydroascorbic acid,the oxidized form of L-ascorbic acid,and subsequently maintained intracellular L-ascorbic acid at higher level and for longer time.On the other hand,AscPNa facilitated the mesenchymal-epithelial transition during reprogramming,downregulated key mesenchymal transcriptional factors like Zeb1 and Twist1,subsequently suppressed the expression of Cyp26a1/b1 which mediates the metabolism of RA,and sustained the intracellular level of RA.Furthermore,the different abilities of RA and AscPNa to induce mesenchymal-epithelial transition,pluripotency,and neuronal differentiation explain their complex contribution to reprogramming when used individually or in combination.Therefore,the current studies identified a positive feedback between RA and AscPNa,or possibility between vitamin A and C,and further explored their contributions to reprogramming.展开更多
基金This work was supported by the National Natural Science Foundation of China(Grant No.31671475,U1601228,31900699,and 81702445)the Strategic Priority Research Program of Chinese Academy of Sciences,No.XDA16010305+3 种基金the Key Research Program of Frontier Sciences of Chinese Academy of Sciences,No.QYZDB-SSW-SMC031the International Partnership Program of Chinese Academy of Sciences,No.154144KYSB20190034the Key Research&Development Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(Grant No.2018GZR110104008)the Science and Technology Planning Project of Guangdong Province(Grant No.2017B030314056)。
文摘Retinoic acid(RA)and 2-phospho-L-ascorbic acid trisodium salt(AscPNa)promote the reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells.In the current studies,the lower abilities of RA and AscPNa to promote reprogramming in the presence of each other suggested that they may share downstream pathways at least partially.The hypothesis was further supported by the RNA-seq analysis which demonstrated a high-level overlap between RA-activated and AscPNa activated genes during reprogramming.In addition,RA upregulated Glut1/3,facilitated the membrane transportation of dehydroascorbic acid,the oxidized form of L-ascorbic acid,and subsequently maintained intracellular L-ascorbic acid at higher level and for longer time.On the other hand,AscPNa facilitated the mesenchymal-epithelial transition during reprogramming,downregulated key mesenchymal transcriptional factors like Zeb1 and Twist1,subsequently suppressed the expression of Cyp26a1/b1 which mediates the metabolism of RA,and sustained the intracellular level of RA.Furthermore,the different abilities of RA and AscPNa to induce mesenchymal-epithelial transition,pluripotency,and neuronal differentiation explain their complex contribution to reprogramming when used individually or in combination.Therefore,the current studies identified a positive feedback between RA and AscPNa,or possibility between vitamin A and C,and further explored their contributions to reprogramming.
