Year 2

The goal of our research is to generate cell lines from neurons with the long term goal to understand how to generate the best possible stem-cell derived models for human neurological diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases. These studies might also reveal basic mechanisms of disease that could inspire new drug development efforts. We proposed to use two cutting edge methods in stem cell biology to accomplish this: cloning and direct reprogramming (generation of induced pluripotent stem cells with reprogramming factors). At the time, methods for direct reprogramming were in their infancy and it was not possible to generate mice entirely from these cells. Because reprogramming neurons is likely to be inefficient and difficult, we proposed to generate entire mice derived from reprogrammed cells. Al cell types, including neurons in these mice would carry special genes to allow us to then turn their neurons into stem cell lines. We have successfully generate such mice and in doing so, we became the first to show that fertile adult mice could be generated from skin cells using induced pluripotent stem cells. This result helps to validate the utility of stem cells and induced pluripotent stem cells and represents the achievement of a critical milestone in our project timeline. Present efforts will use these mice as a unique resource to achieve the goal of the application.