Fig. 4: Iron availability contributes to the regulation of hepatocyte cell fate.
From: A multi-omic approach reveals iron availability influences cell fate fidelity
A Representative immunoblot analysis of HNF4A expression in HepG2 cells cultured in Plasmax, Plasmax-TE, Plasmax-TE+Fe, Plasmax-TE supplemented with copper salts (0.005 µM cupric sulfate), or Plasmax-TE supplemented with iron and copper salts (0.12 µM ferric nitrate, 1.04 µM ferric sulfate, 0.005 µM cupric sulfate). Actin is included as a loading control. B GSEA plots derived from RNA-Seq analysis comparing HepG2 cells cultured in Plasmax-TE with HepG2 cells cultured in Plasmax and comparing HepG2 cells cultured in Plasmax-TE+Fe with HepG2 cells cultured in Plasmax demonstrating signatures associated with hepatocyte cell state and function. Hepatocyte signature, Gene set AIZARANI_LIVER_C14_HEPATOCYTES_2; HNF4A Target genes, Gene set OHGUCHI_LIVER_HNF4A_TARGETS_DN. C Heatmap of hepatocyte and hepatoblast gene expression in Plasmax, Plasmax-TE, or Plasmax-TE+Fe as determined by RNA-Seq analysis, n = 3. D Volcano plot of differentially expressed proteins identified from proteomic analysis comparing HepG2 cells cultured in Plasmax-TE+Fe with HepG2 cells cultured in Plasmax-TE, n = 5. BACH1 targets are highlighted in maroon. Significantly downregulated and upregulated proteins are highlighted in blue and red, respectively. E Representative immunoblot analysis of BACH1 and HNF4A expression in HepG2 cells cultured in EMEM or Plasmax. Actin is included as a loading control. F Schematic demonstrating the reciprocal relationship between iron availability, HNF4A activity, and hepatic fate.
