Year 3

Adult specialized cells can be converted to pluripotent stem cells by activation of specific genes. This process, called induction of pluripotency, opens exciting novel opportunities in Regenerative Medicine. Our goal is to derive and compare new human induced pluripotent stem (iPS) cell lines, in particular to address the question of whether the type of the starting specialized cell affects the properties of the resulting human iPS cells. Beyond this fundamental biological question, our proposed research is also expected to lead to the generation of a significant number of new human iPS cells that will be made available to the scientific community, thus accelerating the pace of research in this field.
We have made significant progress in our proposed goals during the past year. We generated several new human iPS cells from different human specialized cell types and compared them at the cellular and molecular level. Relative to human ES cells, all iPS cells analyzed have significant differences in gene activity that represent a “memory” of original differentiated cell, and we now have a detailed understanding of how this memory is preserved at the level of the organization of the genome. Specifically, it involves the chemical modification (methylation) of DNA at a set of memory genes. We are studying what the significance of this memory is and how much is present in different types of human iPS cells. These results may help optimize methods for derivation and differentiation of human iPS cells. Overall, the progress to date and the planned experiments keep us on track to successfully achieve the goals proposed.