Combined hepatocellular-cholangiocarcinoma derives from liver progenitor cells and depends on senescence and IL-6 trans-signaling

•The combined HCC-CCA tumor originates from hepatic progenitors.•Hepatic progenitors are not the source of HCC.•Combined HCC-CCA initiate on the background of liver inflammation.•Combined HCC-CCA development is dependent on IL-6 trans-signaling.•Senescence contributes to combined HCC-CCA development through IL-6 secretion.