Control of embryonic stem cell metastability by L-proline catabolism

作     者：Laura Casalino Stefania Comes Giuseppina Lambazzi Benedetta De Stefano Stefania Filosa Sandro De Falco Dario De Cesare Gabriella Minchiotti Eduardo Jorge Patriarca 

作者机构：Stem Cell Fate LaboratoryInstitute of Genetics and Biophysics“A.Buzzati-Traverso”CNRNaplesItaly 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2011年第3卷第2期

页      面：108-122页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 10[医学] 

基　　金：This work was supported by Associazione Italiana Ricerca sul Cancro[IG-6128 to G.M.and IG-4840 to S.D.F.] Telethon[GGP-08120 to G.M.] Regione Campania-Programma Operativo Regionale[CRdC WP11 to S.F.,S.D.F,D.D.C.,G.M.and E.J.P.] Ministero Istruzione Universita Ricerca[Medical Research in Italy RBNE08HM7T_003 to E.J.P.] 

主　　题：embryonic stem cells L-proline vitamin C colony phenotype pluripotent states metastability 

摘      要：The molecular mechanisms controlling mouse embryonic stem cell(ESC)metastability,*** capacity to fluctuate between different states of pluripotency,are not fully *** developed and used a novel automation platform,the Cellmaker,to screen a library of metabolites on two ESC-based phenotypic assays(*** and colony phenotype)and identified two metabolically related amino acids,namely L-proline(L-Pro)and L-ornithine(L-Orn),as key regulators of ESC *** compounds,but mainly L-Pro,force ESCs toward a novel epiblast stem cell(EpiSC)-like state,in a dose-and time-dependent *** EpiSCs,L-Pro-induced cells(PiCs)contribute to chimeric embryos and rely on leukemia inhibitor factor(LIF)to ***,PiCs revert to ESCs or differentiate randomly upon removal of either L-Pro or LIF,***,PiC generation depends on both L-Pro metabolism(uptake and oxidation)and Fgf5 induction,and is strongly counteracted by antioxidants,mainly L-ascorbic acid(vitamin C,Vc).ESCs↔PiCs phenotypic transition thus represents a previously undefined dynamic equilibrium between pluripotent states,which can be unbalanced either toward an EpiSC-like or an ESC phenotype by L-Pro/L-Orn or Vc treatments,*** together,our data provide evidence that ESC metastability can be regulated at a metabolic level.