Genetics and Genomics Commons^™

Defining Neuronal Identity Using Microrna-Mediated Reprogramming, Matthew James Mccoy

Arts & Sciences Electronic Theses and Dissertations

Cell fate reprogramming is transforming our understanding of the establishment and maintenance of cellular identity. In addition, reprogramming holds great promise to model diseases affecting cell types that are prohibitively difficult to study, such as human neurons. Overexpression of the brain-enriched microRNAs (miRNAs), miR-9/9* and miR-124 (miR-9/9*-124) results in reprogramming human somatic cells into neurons and has recently been used to generate specific neuronal subtypes affected in neurodegenerative disorders. However, the mechanisms governing the ability of miR-9/9*-124 to generate alternative subtypes of neurons remained unknown. In this thesis, I report that overexpressing miR-9/9*-124 triggers reconfiguration of chromatin accessibility, DNA methylation, …