The goal of this grant is to generate stem cell lines from neurons. This is important because neurons are affected in many diseases yet they cannot be made into dividing cell lines using standard methods and therefore it is difficult to study human neurologic disease. A second goal is to use neuron-derived cell lines to determine whether neurons harbor genomic mutations or stable DNA marks that are relevant to brain development and/or human neurologic disease. We have successfully generated the first mouse pluripotent cell lines that are derived from adult cortical neurons and are in the process of using whole genome sequencing to identify any stable DNA marks that are unique to neurons. Results of this research will help to establish the best methods for modeling human neurological disease using stem cell technologies and establish the extent and identity of stable DNA changes in cortical neurons.