Transcriptional analysis of THs-responding genes during human hepatocyte development

Liver is one of the major targets of thyroid hormones (THs), as well as many industrial chemicals reported as THs-analogues. A number of THs-analogues could permeate the placenta barrier, risking the embryonic development, which may be more susceptible and cause sustained health risk. Therefore, to study the toxicology of industrial chemicals during the hepatocytes developmental stage is necessary, and may be more efficiency. In this study, we differentiated human embryonic stem cells (hESCs) into functional hepatocyte-like cells in presence of two thyroid hormones (THs, T3 and T4), with the purposes trying to dissect genes regulated by THs during human hepatocyte development and identifying biomarkers for THs-analogues. THs exposure finally induced dysfunctional hepatocytes with 19 days differentiation, with impaired glycogen storage ability and lipid droplets accumulation. Global gene expression analysis by RNA-seq identified a number of genes responding to THs were responsible for hepatic differentiation and function, enriched in many metabolic related pathways. Total of 12 samples with 6 groups, including control on day 7 and day 19, T3 treatment on day 7 and day 19, T4 treatment on day7 and day 19; each group contains two replicates.