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Long noncoding RNA (lncRNA) H19 is abundantly expressed in fetal liver. Its expression is significantly diminished in adult healthy liver but is re‐induced in chronic liver diseases, including cholestasis. In this study, we developed a new method with combined   in situ   hybridization (ISH) and immunofluorescence (IF) colabeling to establish an H19 expression profile with both parenchymal and nonparenchymal cell‐specific markers in the livers of cholestatic mouse models and patients with cholestasis.  H19 RNA +  cells showed no colocalization with biliary epithelial cell marker cytokeratin 19 (CK19) +  cholangiocytes but were immediately adjacent to biliary structures in bile duct ligation (BDL), 3,5‐diethoxycarbony1‐1,4‐dihydrocollidine (DDC), and multidrug‐resistant gene 2 knockout (  Mdr2   –/–   ) mouse models and in human primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) liver specimens. In contrast, double‐positive  H19 RNA + /sex‐determining region Y (SRY)‐box 9 (SOX9) +  ductal progenitor cells,  H19 RNA + /hepatocyte nuclear factor 4α (HNF4α) +  hepatocytes,  H19 RNA + /F4/80 +  Kupffer cells, HNF4α + /SOX9 +  hybrid hepatocytes, as well as triple‐positive   H19  RNA + /HNF4α + /SOX9 +  periportal hepatocytes were identified. In addition,   H19  RNA could not be detected in mesenchymal cell marker desmin +  cells. Furthermore,   H19  RNA was predominately detected in cytoplasm with a small amount at the interspace with neighboring cells.   Conclusion:    H19 RNA is localized in HNF4α +  periportal hepatocytes, SOX9 +  ductal progenitor cells, and F4/80 +  Kupffer cells but not in CK19 +  cholangiocytes and desmin +  stellate cells in cholestatic livers.

H19 Is Expressed in Hybrid Hepatocyte Nuclear Factor 4α + Periportal Hepatocytes but Not Cytokeratin 19 + Cholangiocytes in Cholestatic Livers