Directly turning a differentiated cell into a pluripotent cell would be beneficial for producing isogenic replacement cells. It would also present societal benefits by eliminating the use of cells of embryonic or fetal origin. Altering cell fate involves a reprogramming of nuclear function. We have developed an approach for reprogramming cells based on the uptake of regulatory components from a target cell extract by a cell of another type. Nuclear reprogramming probably involves alteration of epigenetic marks, or DNA and histone modifications that allow cells to perpetuate the molecular memory needed to retain their identity.
We propose to investigate the epigenetic basis for “genomic plasticity”, or potential for pluripotency in embryonic and somat ic stem cells. We also wish to explore the extent of genomic plasticity of differentiated cells. We describe a plan to undertake a chromatin characterization in undifferentiated cells and establish whether chromatin organization can account for stem cell pluripotency. Using cell extracts derived from undifferentiated (stem, or stem-like) cells, we will explore the potential of reprogramming differentiated cells to pluripotency and investigate the molecular mechanisms such reprogramming. “Genome-wide” and locus-specific chromatin studies involving combinations of ChIP, PCR and microarray approaches, together with cellular and functional assays will provide a better appreciation of chromatin biology in undifferentiated and differentiated cells. The results might also lead to the development of novel strategies for cell-based therapy.
We have already established an international profile with our studies on nuclear dynamics and nuclear reprogramming. To continue maintaining a high-impact profile and high international standard, we will collaborate with renowned scientists in the areas of stem cell biology, epigenetics, genomics and medicine, and continue publishing in top-rated scientific journals.