Year 1

Specialized cells can be reverted back to induced pluripotent stem cells (iPSCs), and this “reprogramming” holds enormous promise for drug discovery as well as cell transplantation approaches towards the treatment of degenerative diseases. Our goal is to understand the genes and pathways that regulate the process of generation of human iPSCs. During the first year of this award we have made a number of advancements on this front. We have used a large-scale genetic approach to discover new genes and cellular pathways that operate in the specialized cells and act to oppose the process of reprogramming. We have used sophisticated computational biology approaches to gain further insights into these pathways. We have also began the characterization of novel reprogramming barriers at the molecular and cellular level. For example, we have discovered that proteins operating outside of the cell and at the cell surface have unexpected functions in the process of generation of iPSCs. These results keep us on track towards the goal of achieving a deeper understanding of the process of reprogramming human cells to the pluripotent stem cell state.