Transcriptional and Epigenetic Dynamics during Hepatic Specification

Transcriptional and Epigenetic Dynamics during Hepatic Specification The embryonic liver parenchymal cells emerge from the definitive endoderm in response to signals from adjacent mesenchymal and endothelial cells. These bipotent hepatoblasts will differentiate into hepatocytes and cholangiocytes (bile duct cells). While BMP and FGF signalling have emerged as critical in early stages of liver specification, we know little about the differentiation progression of hepatoblasts, the complex relationships between the cell types in the embryonic liver, and how these cells form the intricate structure of the liver. My lab focuses on the transcriptional mechanisms regulating hepatic differentiation. To explore early liver development, we are using single cell analysis in mouse liver bud formation and whole genome epigenetic approaches in human pluripotent stem cells (hPSCs) differentiated along the hepatic lineage. Our single cell analysis has allowed us to explore the cell lineage diversity in the early liver bud which provides a comprehensive atlas of liver lineage establishment from the endoderm and mesoderm through to the organization of the primitive sinusoid at single-cell resolution. In addition, our hPSC differentiation studies have identified the complex transcriptional dynamics which drive differentiation of the major hepatic lineage and offer mechanistic understanding into the complexity liver formation.