Positive feedback between retinoic acid and 2-phospho-L-ascorbic acid trisodium salt during somatic cell reprogramming

作     者：Mengdan Zhang Qian Li Tingting Yang Fei Meng Xiaowei Lai Lining Liang Changpeng Li Hao Sun Jiaqi Sun Hui Zheng 

作者机构：CAS Key Laboratory of Regenerative BiologyGuangzhou Institutes of Biomedicine and HealthChinese Academy of Sciences#190 Kaiyuan Ave.Science CityGuangzhou 510530Huangpu DistrictChina Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory)Guangzhou 510700China Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineGuangzhou 510530China University of Chinese Academy of SciencesBeijing 100049China Guangzhou Medical UniversityGuangzhou 511436China Institutes for Stem Cell and RegenerationChinese Academy of SciencesBeijing 100101China 

出 版 物：《Cell Regeneration》 (细胞再生（英文）)

年 卷 期：2020年第9卷第1期

页      面：180-189页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

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 the Key Research Program of Frontier Sciences of Chinese Academy of Sciences,No.QYZDB-SSW-SMC031 the International Partnership Program of Chinese Academy of Sciences,No.154144KYSB20190034 the 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) 

主　　题：Reprogramming L-ascorbic acid Retinoic acid Positive feedback Mesenchymal-epithelial transition 

摘      要：Retinoic acid(RA)and 2-phospho-L-ascorbic acid trisodium salt(AscPNa)promote the reprogramming of mouse embryonic fibroblasts to induced pluripotent stem *** 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 *** hypothesis was further supported by the RNA-seq analysis which demonstrated a high-level overlap between RA-activated and AscPNa activated genes during *** 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 *** 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 ***,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 ***,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.