Consistently, in the nontumorous tissues in the Numb−/− livers, progenitor markers (Sox9, CD133, and CD24) and cell cycle proteins (CDK1 and CDK2) were significantly upregulated (Fig. 3G), further demonstrating that Numb deficiency promotes the expansion and malignant transformation of HPCs upon carcinogen challenge, which ultimately leads to the occurrence of iCCA. This evidence concerns the gene SOX9 and infantile convulsions and choreoathetosis.