Characterization of the Dedifferentiated Schwann Cell and Development of a Deprogramming-Strategy to Enhance Their Regenerative Capacity

Abstract

A striking feature of the peripheral nervous system is the ability to regenerate; this ability is, in part, due to the Schwann cell, the glial cell of the periphery. Following peripheral injury, Schwann cells up-regulate a battery of proteins, many of which are re-expressed from development, that drive the efficient regenerative response in the peripheral nervous system. My work described in this thesis characterizes the gene expression profile driving this regenerative response as well as factors implicated during Schwann cell development. Then, I began to develop a deprogramming-based approach to modulate the Schwann cell phenotype by overexpressing the factors of interest. I optimized a deprogramming strategy that can be used to further elucidate the functional contribution of various transcription factors in adult Schwann cells. This can also enhance Schwann cell function following circumstances such prolonged denervation, disease, or advanced aged which often results in impaired regenerative function.