Stem Cells: Pluripotency and Nuclear Reprogramming

The recent demonstration of in vitro reprogramming using transduction of 4 transcription factors by Yamanaka and colleagues represents a major advance in the field. Direct reprogramming of somatic cells into induced pluripotent stem (iPS) cells can be achieved by over-expression of the Oct4, Sox2, Klf4 and c-Myc transcription factors. This approach will allow the generation of patient specific iPS cells that can be used to study complex human diseases in the Petri dish. Progress in using iPS cells for therapy and for the study of complex human diseases will be summarized. The presence of reprogramming vectors in the iPS cells and the inefficiency of gene targeting represent two important impediments for realizing the potential of ES and iPS cells to study human diseases. We have designed strategies that efficiently allow the generation of vector-free iPS cells. In addition, we have used Zn finger mediated genome editing to establish efficient protocols to target expressed as well as silent genes in human ES and iPS cells.