A multi-omic approach reveals iron availability influences cell fate fidelity

Abstract

Recent evidence has highlighted the importance of employing culture media designed to emulate the metabolic environment Here, we utilize the physiological medium Plasmax to examine the impact of nutrient availability on the human hepatocyte cell line, HepG2. Incubation of HepG2 cells in Plasmax suppressed a transcriptional program driven by Hepatocyte Nuclear Factor 4 (HNF4A), a master regulator of hepatocyte identity. Given that HepG2 cells were originally isolated from a patient with hepatoblastoma, this suggests reversion to the native state in physiological media. Importantly, exclusion of iron from Plasmax reinstated the HNF4A-driven transcriptional program. These studies suggest a relationship between iron availability and the fidelity of hepatocyte cell fate and highlight the importance of more faithfully recapitulating in vivo metabolite availability in vitro.