Redox-based Epigenetic Changes Contribute to Defining Neuronal Stem Cell Fate

Grant Winners

Deans

Abstract

​What defines Neurons and what are the underlying mechanisms that define neuronal cell fate?, are some of the questions that will be investigated during the course of the proposed work. Low oxygen concentrations (hypoxia) occur in several physiological and pathological cellular situations such as embryogenesis and stem cell proliferation. Any changes in this redox status can mediate changes in the neuronal developmental trajectory. The mechanism through which such changes occur in the neuronal development and neuronal stem cell differentiation is still unknown. This is highly important especially since the environmental factors including exposure to pesticides and insecticides as well as alcohol and other drugs can lead to altered redox status and induce oxidative stress, eventually leading to altered neuronal development and skewed developmental trajectory. We will manipulate the redox status and investigate the effects on neuronal differentiation. We will also investigate the changes in underlying gene expression and gene regulation that could contribute to changes in the neuronal fate and neuronal differentiation. Epigenetic status are an epiphenomenon that are highly critical for the differentiation of stem cells into different types of cells. Since our previous studies report that redox status is tightly regulated to epigenetic status, we hypothesize that epigenetic changes under the influence of altered redox status are one such mechanism to alter the neuronal development. While the short term goal is to identify the effects of altered redox status on the altered epigenetic status in neuronal stem cells; the long term goal is to identify functional gene pathways that contribute to defining neuronal cell fate under the influence of redox status. Such functional pathways could contribute to neurodevelopmental disease and could be used as target.