Extended Data Figure 6. Characterization of response to liver injury in GEM model with hepatocyte-specific mutant IDH expression.

Tet-R140Q or Tet-R172K mice and littermate controls (WT) receiving Dox were fed a DDC-containing diet for 5 days before being switched to normal chow for 7 or 21 days (See main text, Fig. 3a for schematic).

a. Representative H&E images of livers from WT and Tet-R140Q mice analyzed at day 7 and 21.

b. Quantification of Ki67-positive cells for indicated markers as shown in main text, Fig. 3e (N = 3 mice per group, from at least 5 high-powered field per mouse scored). Error bars, ±s.e.m. Data from Fig. 3f (day 21) is reproduced here for comparison.

c, d.IF analysis of IDH2 mutant livers showing that Ki-67 co-localizes with HNF4α (c) and R140Q-expressing cells (d). As shown in main text, Fig. 3e, these cells express lower levels of HNF4α compared to WT hepatocytes.

e, f. Tet-R172K mice and littermate controls (WT) receiving Dox were fed a DDC-containing diet for 5 days before being switched to normal chow for 1 week. IF analysis of IDH2 mutant livers shows that Ki-67 co-localizes with HNF4α and R172K-expressing cells (e) and greater numbers of Ki-67⁺,HNF4α⁺ cells in Tet-R172K compared to WT mice (f).

Error bars indicate ±s.e.m. between 3 mice; Scale bars, 50µm. Student’s t-test * P<0.05.