Year 3

Our overarching goal is to understand the mechanisms controlling the balance between stem cell pluripotency, self-renewal, and tumorigenesis, to harness the full therapeutic promise of human embryonic stem cells (hESCs). To this end, we study the function of the RB gene family in stem cells. Our initial hypothesis was that RB family genes may control the reprogramming of somatic cells into iPSCs by interacting with chromatin remodeling factors to induce specific changes in the chromatin structure and control the expression of a specific program of genes. We found that loss of RB, but not of its family members p107 and p130, results in enhanced reprogramming of fibroblasts to iPS cells. In the past year, we have investigated this unique function of RB. In particular, we have performed high throughput RNA-seq and ChIP-seq experiments for RB early in the differentiation process to explore the mechanisms by which loss of RB may enhance reprogramming. We have also performed ChIP-Seq experiments with various chromatin marks to explore the relationship between RB loss and change sof the chromatin structure of cells early in reprogramming.