Molecular Mechanisms Regulating Somatic Reprogramming

In reprogramming, cellular transition to pluripotency only occurs in few cells. My thesisis focused on exploring the mechanisms underlying the successful transition of somatic cells to pluripotent stem cells. Our lab has previously reported reprogramming as a multistep process characterized by initiation, maturation, and stabilization phases based on temporal changes in gene expression. The stabilization phase marks the successful acquisition of pluripotency. Using a functional RNAi screen targeting genes specificallyenriched in cells poised to become pluripotent, I show that distinct molecular networks control the acquisition and subsequent maintenance of pluripotency. Furthermore, I also reveal the functional role of a new class of RNAs, called long intergenic noncoding RNAs (lincRNAs), in the mesenchymal-to-epithelial transition during the initiation phase. Next, I present a novel mouse piggybac primary reprogramming system that ismore robust and efficient than the conventional mouse secondary reprogramming systems and illustrate its utility for mechanistic studies.M.Sc