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 cells would be exposed to in vivo. Here, we utilize the physiologic 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, leading to a dedifferentiated phenotype. Given that HepG2 cells were originally isolated from a patient with hepatoblastoma, this suggested reversion to the native state in physiologic medium. Importantly, exclusion of iron from Plasmax reinsta..