CHROMATIN ACCESSIBILITY CHANGES DURING ADIPOSE BEIGING AND MELANOCYTE STEM CELL ACTIVATION

Abstract

The study of chromatin accessibility has been fundamentally important to understand gene regulatory networks underlying cellular behavior. I performed a single-nucleus assay for transposase-accessible chromatin (snATAC-seq) to characterize the changes in cellular heterogeneity and chromatin accessibility during adipose beiging and melanocyte stem cell activation. In the first part of my thesis research, by applying snATAC-seq on adipose tissue, I identified distinct cell types in adipose tissue. I found substantial changes in adipocytes with an increase in abundance of beige adipocytes in response to thermogenic stimuli. I characterized a gene regulatory network during adipose beiging and identified commonality and heterogeneity of gene programs activated by two major thermogenic stimuli. In the second part of my dissertation, I aimed to characterize melanocyte stem cells and their progeny and delineate the mechanisms and key regulators in melanocyte stem cell activation. By applying snATAC on sorted melanocytes, I identified three major cell states and characterized their chromatin states. The cell states vary by hair follicle cycles and environmental cues. I revealed potential regulators for activation of stem cell fate. Our data provide insights into cellular heterogeneity and gene regulatory networks underlying changes of cellular behaviors by analyzing chromatin states at a single-cell level.