Cdkn1a

Hepatocyte-specific SOCS1-deficient mice (Socs1^fl/flAlb^Cre) were previously described [4 (link)]. Socs3^fl/fl, Alb^Cre, Cdkn1a^−/−, and p53^−/− mice were purchased from the Jackson Laboratory. Mice lacking SOCS3, SOCS1, and SOCS3 in hepatocytes (Socs3^fl/fAlb^Cre; Socs1^fl/flSocs3^fl/flAlb^Cre) were generated for this study. Socs1^fl/flAlb^Cre mice were crossed with Cdkn1a^−/− or Tp53^−/− to generate SOCS1-deficient mice also lacking CDKN1A (Socs1^fl/flAlb^CreCdkn1a^−/−) or p53 (Socs1^fl/flAlb^CreTp53^−/−) in hepatocytes. All mice strains used in this study are in C57BL/6N background and are listed in Supplementary Table S1. Control mice were derived from littermates. Mice were housed in ventilated cages with 12 h day/night cycle and fed with normal chow ad libitum. All experiments on mice were carried out during the daytime with the approval of the Université de Sherbrooke Ethics Committee for Animal Care and Use (Protocol ID 226-17B; 2017-2043).

Conditional Ezh2 knockout mice (loxP-flanked Ezh2 allele, Ezh2^fl/fl, C57BL/6) were a generous gift of Dr. Alexander Tarakhovsky, The Rockefeller University^{10 (link)}. By crossing Ezh2^fl/fl with the transgenic Cγ1-cre strain (C57BL/6) we generated heterozygous Ezh2^fl/WT mice, which were crossed to obtain Ezh2^fl/fl mice. These mice were crossed to Cdkn1a^−/− (B6129SF2/J) to obtain Ezh2^fl/WT;Cγ1-cre⁺;Cdkn1a^-/+ heterozygous, which were further crossed to yield Ezh2^fl/fl;Cγ1-cre⁺;Cdkn1a^−/− double knockout (mixed B6;129 background). As control groups, we used Ezh2^fl/fl;Cγ1-cre negative and the single knockouts Ezh2^fl/fl;Cγ1-cre⁺ and Cdkn1a^−/− littermates (mixed B6;129 background). The following strains were purchased from The Jackson Laboratory: Cγ1-cre (010611), Cdkn1a^−/− (003263), E2f1^−/− (002785), B6129SF2/J (101045), and C57BL6 (000664).
Animal care was in strict compliance with institutional guidelines established by the Weill Cornell Medical College, the Memorial Sloan-Kettering Cancer Center, the Guide for the Care and Use of Laboratory Animals (National Academy of Sciences 1996)³⁷ , and the Association for Assessment and Accreditation of Laboratory Animal Care International.