DISSECTING PLURIPOTENCY IN STEM CELLS

Abstract

THE ECTOPIC EXPRESSION OF TRANSCRIPTION FACTORS (TFS) CAN REPROGRAM SOMATIC CELLS BACK TO A PLURIPOTENT FATE. ALTHOUGH SEVERAL FACTORS THAT AUGMENT THE EFFICIENCY OF INDUCED PLURIPOTENT STEM CELL (IPSCS) FORMATION HAVE BEEN INDIVIDUALLY DISCOVERED, INCOMPLETE KNOWLEDGE OF THE MOLECULAR MECHANISMS AT WORK CONTINUES TO HAMPER EFFORTS TO MAXIMISE REPROGRAMMING YIELD AND EFFICIENCY. HERE, I PRESENT THE FIRST SYSTEMATIC GENOME-WIDE RNA INTERFERENCE SCREEN TO DETERMINE THE GLOBAL CONTROLS DURING THE EARLY STAGES OF THE REPROGRAMMING PROCESS. THE SCREEN IDENTIFIES KEY FUNCTIONAL REPRESSORS AND EFFECTORS WHICH IMPEDE OR PROMOTE THE ACQUISITION OF PLURIPOTENCY. I OBSERVED FOUR STRIKING ASPECTS FROM OUR STUDY. FIRSTLY, REPRESSORS AND EFFECTORS FORM CLOSE INTERACTING NETWORKS. SECONDLY, THE SIMULTANEOUS REMOVAL OF TWO OR MORE REPRESSORS GREATLY ENHANCED REPROGRAMMING. THIRDLY, CHIP-SEQ ANALYSES REVEALED THAT OCT4, SOX2, KLF4 AND C-MYC (OSKM) BOUND EXTENSIVELY TO REPRESSOR AND EFFECTOR GENE LOCI