Article MicroRNA-302/367ClusterGovernshESCSelf-RenewalbyDuallyRegulating Cell Cycle and Apoptosis Pathways

SUMMARY miR-302/367isthemostabundantmiRNAclusterinhumanembryonicstemcells(hESCs)andcanpromotesomaticcellreprogramming.However,itsroleinhESCsremainspoorlyunderstood.Here,westudiedfunctionalrolesoftheendogenousmiR-302/367clusterinhESCsby employing specific TALE-based transcriptional repressors. We revealed that miR-302/367 cluster dually regulates hESC cell cycle andapoptosis in dose-dependent manner. Gene profiling and functional studies identified key targets of the miR-302/367 cluster in regu-latinghESCself-renewalandapoptosis.Wedemonstratethatinadditiontoitsroleincellcycleregulation,miR-302/367clusterconquersapoptosis by downregulating BNIP3L/Nix (a BH3-onlyproapoptotic factor) and upregulating BCL-xL expression.Furthermore, we showthat butyrate, a natural compound, upregulates miR-302/367 cluster expression and alleviates hESCs from apoptosis induced by knock-downofmiR-302/367cluster.Insummary,ourfindingsprovidenewinsightsinmolecularmechanismsofhowmiR-302/367clusterreg-ulates hESCs. INTRODUCTION