Grant: Operating Grant

The differentiation potential captured within cultures of human pluripotent stem cells (hPSCs) have driven expectations that these cells will provide a model for insights into human development and a resource for the production of tissues compatible with therapeutic transplantations. Human PSCs have until recently only been accessible by harvesting them from the early embryo, but a recent exciting discovery has revealed that hPSCs can be generated by "reprogramming" cells in the adult body. Harnessing the potential of hPSCs requires understanding how pluripotency is gained during reprogramming, maintained and then lost during the process differentiation into adult tissues. Although some of the major players that control pluripotency have been identified, our understanding of pluripotency in hPSCs is largely based on studies of mouse PSCs, which show a number of differences with their human counterparts. Our laboratory has made human cell lines that report the expression of the pluripotency associated gene REX1 and revealed two previously unappreciated populations in seemingly uniform PSCs. These two populations appear to represent steppingstones in the process of differentiation into tissues that could have therapeutic potential in the clinic. We are proposing to studying how entry and exit through the stages that these populations represent can be manipulated to provide greater control of cellular fate. We anticipate that advances arising from our work will have direct relevance to human health via the generation of cells and tissues amenable to drug screening and transplantation.