Molecular determinants of accurate differentiation from human pluripotent stem cells

For human pluripotent stem cells to reach their full potential in cell based therapeutics it is absolutely essential that their differentiation to particular cell types produces a product with the functional capacity to replace lost tissue. As California is a leader in the adoption of pluripotent stem cell therapies, it is vital that it also be a leader in the generation of derivatives from pluripotent stem cells that accurately mimic cells found in tissue. Our data suggests that instead of generating cells that would normally be found in adult tissue, human pluripotent stem cells instead produce cells found during very early fetal development. Not only does this suggest that cell based therapies with such cells might be hampered, but in fact the proliferative nature of these cells could even make them dangerous. We propose a series of experiments that will test the idea that manipulating the gene expression of pluripotent derivatives during differentiation will make cells that more accurately reflect those found in tissues that would typically require stem cell based treatments. We will develop tools that will be easily applicable for a wide range of cell types and yield mature, functional cells that not only mimic tissue derived cells, but can also functionally replace cells that are lost in disease or injury. This work will be particularly beneficial to ongoing efforts in California to apply pluripotent stem cells in therapeutic settings, and will therefore greatly benefit Californians requiring such treatment.