A multi-omic approach reveals iron availability influences cell fate fidelity
- Author(s)
- Ong, AJS; Tigani, TA; Gomes, AJ; Reinecke, JM; Cox, AG; Brown, KK;
- Details
- Publication Year 2026-03-06,Volume 4,Issue #1,Page 11
- Journal Title
- NPJ Metabolic Health and Disease
- Publication Type
- Research article
- 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 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.
- Publisher
- Springer Nature
- Department(s)
- Laboratory Research
- Publisher's Version
- https://doi.org/10.1038/s44324-026-00102-8
- Open Access at Publisher's Site
https://doi.org/10.1038/s44324-026-00102-8- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-03-31 11:33:31
Last Modified: 2026-03-31 11:33:37