Proteomics

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

ABSTRACT: Recent evidence has highlighted the importance of employing cell culture media designed to reproduce the physiological metabolic environment in vitro. Here, we utilize the physiological medium Plasmax to examine the impact of nutrient availability on the model 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 the trace element iron from Plasmax reinstated the HNF4A-driven transcriptional program. Taken together, these studies suggest a relationship between iroN availability and regulation of hepatocyte cell fate and highlight the importance of more faithfully recapitulating in vivo metabolite availability in vitro.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte

SUBMITTER: Kristin Brown  

LAB HEAD: Kristin K Brown

PROVIDER: PXD060175 | Pride | 2026-03-16

REPOSITORIES: Pride

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

Ong Athena Jessica S AJS   Tigani Tara A TA   Gomes Adele J AJ   Reinecke Jordyn M JM   Cox Andrew G AG   Brown Kristin K KK  

npj metabolic health and disease 20260306 1

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. Giv  ...[more]

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