09: Inducing Pluripotency with MiRNAs: New Paradigm Shif in Cell Reprogramming

Stanford University, Stanford CA

Investigators

Linked publications & trials

Abstract

Successful reprogramming of adult human fibroblast cells into iPS cells based on transcription factors has now been reported independently by Shinya Yamanaka in Kyoto University, Japan (Oct 3/4. Sox2, Klf4, c-Myc) 4 and James Thomson in University of Wisconsin (Oct4, Sox2, Nanog, Lin28) 5. More recently, Yamanaka's group has also shown that c-Myc is not necessary for the generation of transcription factor-iPS (TF-iPS) cells from mouse and human fibroblasts 6. The main advantage of this approach is that it does not need human embryos or oocytes to generate patient-specific stem cells, and therefore can potentially bypass the ethical and political debates that have surrounded this field for the past decade. Another important advantage is that for the first time, disease-specific stem cells can be created, which will help us understand the molecular mechanisms of many common inherited diseases. Though there is some evidence suggesting miRNAs can drive cell fate, so far there is no proof that they can do the reverse and drive pluripotency. Interestingly, one study has shown that Lin28, one of the reprogramming factors used by the Thomson lab, blocks a specific miRNA (pri-let-7) that is preferentially expressed in adult cells, suggesting one possible mechanism of induction of pluripotency in adult cells 16. With this new knowledge of miRNAs, I propose an entirely different and novel method for reprogramming adult cells into iPS cells, one that involves over-expression of selected miRNA via a novel non-viral vector system.[unreadable]