Epigenetic Regulation in Human Embryonic Stem Cell Lineage Specification

Embryonic development is a complex and intricately timed process such that any deviation from the correct sequence of events can elicit unwanted developmental effects. Epigenetic mechanisms, like DNA methylation and microRNAs (miRNAs), have a crucial role in development, impacting gene expression in the cell necessary for tissue-specific gene expression, gene-environment interactions, differentiation, and growth. Human embryonic stem cells (hESCs) have helped our understanding of mechanisms involved in development and disease. Yet, the epigenetic factors involved in early hESC differentiation before specialized cell types need further understanding. My research program seeks to investigate the relationship between DNA methylation and miRNAs during early hESC lineage specification. We will dissect early cell fate changes due to epigenetic regulation using various omics technologies, cell imaging, and transcriptional regulator expression changes. We will explore the interplay between DNA methylation and miRNAs to regulate gene expression during normal and abnormal differentiation. In addition, we will answer questions about the most suitable methods for directed differentiation and cell state identity, such as determining the cell makeup in a pan-mesoderm differentiation approach and using methods that differentiate cells through a specific mesoderm subtype. We are excited about the proposed work and believe our projects will contribute to understanding of embryogenesis, stem cell biology, and identifying epigenetic factors leveraged as biomarkers of aberrant embryonic development.