A Crucial Role of Hepatocyte Nuclear Factor-4 Expression in the Differentiation of Human Ductular Hepatocytes

Hakoda, Tomomi; Yamamoto, Kazuhide; Terada, Ryo; Okano, Nobuaki; Shimada, Noriaki; Suzuki, Tsuyoshi; Mizuno, Motowo; Shiratori, Yasushi

doi:10.1097/01.lab.0000092229.93203.57

Cited by 12 publications

(7 citation statements)

References 19 publications

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“…In addition to its nuclear localization in hepatocytes, HNF4α was highly expressed in the cytoplasmic compartment in DR and fibrotic areas (white arrow). Prior studies showed cytoplasmic expression of HNF4α messenger RNA in ductular hepatocytes in massive necrosis areas . The subcellular localization of HNF4α could be associated with its phosphorylation status .…”

Section: Resultsmentioning

confidence: 95%

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

Jiang

Huang

Cai

et al. 2018

Hepatology Communications

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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. H19RNA+ 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 H19RNA+/sex‐determining region Y (SRY)‐box 9 (SOX9)+ ductal progenitor cells, H19RNA+/hepatocyte nuclear factor 4α (HNF4α)+ hepatocytes, H19RNA+/F4/80+ Kupffer cells, HNF4α+/SOX9+ hybrid hepatocytes, as well as triple‐positive H19RNA+/HNF4α+/SOX9+ periportal hepatocytes were identified. In addition, H19RNA could not be detected in mesenchymal cell marker desmin+ cells. Furthermore, H19RNA was predominately detected in cytoplasm with a small amount at the interspace with neighboring cells. Conclusion: H19RNA 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.

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Section: Resultsmentioning

confidence: 95%

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

Jiang

Huang

Cai

et al. 2018

Hepatology Communications

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“…An extensive ductular reaction occurs after massive (or submassive) hepatic necrosis in humans 47–53. In this type of injury, ductular proliferation involves mature cholangiocytes and ductular hepatocytes.…”

Section: Oval Cell Differentiation In Massive Hepatic Necrosis In Humansmentioning

confidence: 99%

Liver regeneration and repair: Hepatocytes, progenitor cells, and stem cells

2004

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S tudies of liver regenerative processes have gained new prominence, generated from analyses of genetically engineered animal models, the transplantation of human livers, and the surging interest in stem cells. These studies gave rise to expectations regarding the practical applications of research on the mechanisms of liver regeneration that were unthinkable just a few years ago. As the field expanded to a broader audience, this new knowledge also brought confusion and often misinterpretations regarding the cellular mechanisms responsible for liver regeneration in different types of hepatic growth processes. This article is a brief review of the role of hepatocytes, oval cells (see box for nomenclature), and bone marrow cells in liver regeneration and repopulation. This topic has generated great excitement, a good deal of noise, much controversy, and many surprises. The review of the rapidly expanding literature presented here, particularly as it deals with stem cells, was guided by a few principles: (1) be wary of dogma 1 and of overinterpretation of data; (2) a "new discovery" may be a true new finding, but it may simply be the repackaging of an old discovery; and (3) an exciting story is not necessarily a true story.

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“…It has been reported that the HNF6 and HNF1β are important in biliary development, 15 while HNF1α and HNF4α are important in hepatocyte specification. 16,17 We assessed biliary and hepatic marker expression by quantitative PCR. We observed significant upregulation in HNF6 expression on PU134 and laminin (both 1.6-fold induction, p <0.001), and in HNF1β expression (1.4-fold, p <0.001; and 1.6-fold, p <0.05, respectively) when compared to the plastic controls (Fig.…”

Section: Resultsmentioning

confidence: 99%

Maintaining Hepatic Stem Cell Gene Expression on Biological and Synthetic Substrata

Lucendo

Khan

Pernagallo

et al. 2012

BioResearch Open Access

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The liver is a highly resilient organ that possesses enormous regenerative capacity. This is mediated mainly through the most abundant cell type found in the liver, the hepatocyte. When the regenerative capacity of the hepatocyte is compromised, during chronic or acute liver injury, hepatic progenitor cells (HPCs) are activated to replace the damaged tissue. The HPC resides in a laminin-rich environment; as HPCs differentiate toward a hepatic or biliary fate, the extracellular matrix (ECM) composition changes, influencing cell behavior. To assess the impact that the biological ECM and the synthetic ECM have on the maintenance of hepatic stem cell gene expression, a murine hepatic stem cell line was employed. We demonstrate that hepatic stem cell gene expression could be maintained using a biological or synthetic substratum, but not on plastic alone.

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A Crucial Role of Hepatocyte Nuclear Factor-4 Expression in the Differentiation of Human Ductular Hepatocytes

Cited by 12 publications

References 19 publications

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

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

Liver regeneration and repair: Hepatocytes, progenitor cells, and stem cells

Maintaining Hepatic Stem Cell Gene Expression on Biological and Synthetic Substrata

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