Fig 1: Renal parenchymal cell ferroptosis is critical for metformin-aggravated nephrotoxicity.a Representative image of kidneys removed from mice in the indicated groups. Where indicated, the mice received metformin (100 mg/kg), Fer-1 (1 mg/kg), Nec-1 (1 mg/kg), or Emr (2.5 mg/kg). b Summary of the kidney to body weight ratio measured in the indicated mice. c–f Summary of serum BUN (c), creatinine (d), LDH (e), and AST (f) measured in the indicated mice. g Summary of renal Lcn2 mRNA levels measured in the indicated mice. h Summary of renal MDA levels measured in the indicated mice. i Representative H&E-stained, Sirius Red-stained, and Masson’s Trichrome-stained kidney sections from the indicated mice. j Summary of significantly differential pathways in the indicated parenchymal cell types of I/R+Met200 vs I/R. k t-SNE reveals clustering of 69,608 renal cells obtained from mice in the I/R group (n = 2), I/R+Met200 group (n = 2), and I/R+Met200+Fer-1 group (n = 2). l. t-SNE reveals 14 distinct cell types in the kidney. m Annotation of renal cells in I/R, I/R+Met200 and I/R+Met200+Fer-1 groups. n Summary of the number of cells included in the scRNA-seq analysis for the indicated groups (n = 2 mice per group), expressed relative to the Sham. o Summary of the percentages of the indicated cell types in the indicated groups. p Summary of the percentage of the indicated renal parenchymal cell types in 4 groups shown at the left. q Electron micrographs showing the cellular morphology of renal tubular epithelial cells in the indicated groups. *P < 0.05, **P < 0.01, ***P < 0.001, and n.s., not significant (One-way ANOVA). See also Supplementary Figs. S5–S8.