Figure 1 from SALL4 Is Required for YAP1-Dependent Malignant and Regenerative Hepatocyte-to-Cholangiocyte Reprogramming

<p>SALL4 is specifically required for <i>YAP1</i>-mediated HC-to-CCA transformation. <b>A,</b> qRT-PCR analysis showing the relative expression levels of <i>Sall4</i> in different murine liver tumor models [<i>AY</i>-CCA, <i>ANRAS</i>-combined HCC–CCA, <i>KP53</i>-mixed HCC–CCA, and <i>β</i>-catenin (<i>β</i>-cat)-driven HCCs]. <b>B,</b> Schematic representation of the experimental design. HDTVI was used to deliver oncogenes (<i>AY</i>: <i>myrAkt-HA</i> + <i>YAP1</i><sup><i>S127A</i></sup>; <i>ANRAS</i>: <i>myrAkt-HA</i> + <i>NRAS</i><sup><i>G12V</i></sup>; <i>KP53</i>: <i>KRAS</i><sup><i>G12D</i></sup><i>+ shp53</i>) into <i>Sall4</i><sup><i>fl/fl</i></sup> mice, combined with a prior intravenous injection (2 weeks before HDTVI) of <i>AAV8-TBG-GFP</i> (<i>Sall4 WT</i><sup><i>GFP</i></sup>) or <i>AAV8-TBG-Cre</i> (<i>Sall4 KO</i><sup><i>hepΔ</i></sup>). Livers were analyzed 4 to 6 weeks after HDTVI. <b>C,</b> Representative liver images from each model (<i>AY</i>, <i>ANRAS</i>, and <i>KP53</i>) comparing <i>Sall4 WT</i><sup><i>GFP</i></sup> and <i>Sall4 KO</i><sup><i>hepΔ</i></sup>. <b>D,</b> LW/BW ratio analysis across all models comparing <i>Sall4 WT</i><sup><i>GFP</i></sup> and <i>Sall4 KO</i><sup><i>hepΔ</i></sup> (<i>n</i> = 3–4 mice per group). <b>E,</b> IHC for panCK (CC lineage marker) and HNF4A (HC lineage marker). <b>F,</b> Quantification of panCK<sup>+</sup> area (%) in <i>ANRAS</i> and <i>KP53</i> livers. <b>G,</b> IHC for HA-tag and the proliferation marker Ki-67 in <i>AY</i> tumors from <i>Sall4 WT</i><sup><i>GFP</i></sup> and <i>Sall4 KO</i><sup><i>hepΔ</i></sup> mice. Data are presented as the mean ± SD; Student <i>t</i> test (**, <i>P</i> < 0.01; ***, <i>P</i> < 0.001; ns, not significant). Scale bars, (<b>E</b>) 200 μm; <b>G,</b> 1 mm (overview), 200 μm (magnified views).</p>