The function of hepatocytes largely depends on their position in the liver lobule. Although the method of differentiating hepatocytes from human pluripotent stem cells has been largely improved over the past decade, there remains no technique for generating hepatocyte-like cells (HLCs) with zone-specific hepatic properties. In this study, we searched for the factors that promote acquisition of zone-specific properties of HLCs. Here, we identified that WNT7B and WNT8B secreted from hepatocytes and cholangiocytes play important roles in achieving perivenous zone-specific characteristics, such as the enhancement of glutamine secretion, citric acid cycle, cytochrome P450 (CYP) 1A2 metabolism, and CYP1A2 induction capacities. We also found that WNT inhibitory factor (WIF-1) secreted from cholangiocytes was necessary for achieving periportal zone-specific characteristics, such as the enhancement of urea secretion and gluconeogenesis capacities. Therefore, WNT signal modulators secreted from hepatocytes or cholangiocytes conferred zone-specific hepatic properties onto HLCs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5475257 | PMC |
| http://dx.doi.org/10.1016/j.ymthe.2017.04.006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Self-Assembled Generation of Multi-zonal Liver Organoids from Human Pluripotent Stem Cells.
bioRxiv
August 2024
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.
Distinct hepatocyte subpopulations are spatially segregated along the portal-central axis and critical to understanding metabolic homeostasis and liver injury. While several bioactive molecules have been described to play a role in directing zonal fates, including ascorbate and bilirubin, replication of zonal liver architecture has not been achieved to date. In order to evaluate hepatic zonal polarity, we developed a self-assembling zone-specific liver organoid culture by co-culturing ascorbate and bilirubin enriched hepatic progenitors derived from human induced pluripotent stem cells.
View Article and Find Full Text PDFMitoTracker Red for isolation of zone-specific hepatocytes and characterization of hepatic sublobular metabolism.
Biochem Biophys Res Commun
November 2024
Department of Drug Discovery & Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address:
Background: The liver lobule is divided into three zones or regions: periportal (PP or Zone 1) that is highly oxidative and active in ureagenesis, pericentral (PC or Zone 3) that is more glycolytic, and midzonal (MZ or Zone 2) with intermediate characteristics.
Aim: Our goal was to isolate and metabolically characterize hepatocytes from specific sublobular zones.
Methods: Mice were administered rhodamine123 (Rh123) or MitoTracker Red (MTR) prior to intravital imaging, liver fixation, or hepatocyte isolation.
Spatial lipidomics reveals zone-specific hepatic lipid alteration and remodeling in metabolic dysfunction-associated steatohepatitis.
J Lipid Res
September 2024
Institute of Clinical Chemistry, Inselspital, Bern University Hospital, Bern, Switzerland. Electronic address:
Alteration in lipid metabolism plays a pivotal role in developing metabolic dysfunction-associated steatohepatitis (MASH). However, our understanding of alteration in lipid metabolism across liver zonation in MASH remains limited. Within this study, we investigated MASH-associated zone-specific lipid metabolism in a diet and chemical-induced MASH mouse model.
View Article and Find Full Text PDFGlycolysis in hepatic stellate cells coordinates fibrogenic extracellular vesicle release spatially to amplify liver fibrosis.
Sci Adv
June 2024
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
Article Synopsis
- Liver fibrosis involves the activation of hepatic stellate cells (HSCs) and the release of extracellular vesicles (EVs), with increased glycolysis in HSCs playing a key role in this process.
- Genetic inhibition of glycolysis in HSCs was shown to reduce liver fibrosis and alter the expression of EV-related pathways specifically in the liver's pericentral zone.
- The study suggests that targeting glycolysis in HSCs could serve as a new therapeutic approach to mitigate liver fibrosis by decreasing the release of fibrogenic EVs.
Spatial transcriptomics unravels palmitoylation and zonation-dependent gene regulation by AEG-1 in mouse liver.
J Biol Chem
June 2024
Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, USA; Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA; VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, Virginia, USA. Electronic address:
Obesity-induced metabolic dysfunction-associated steatohepatitis (MASH) leads to hepatocellular carcinoma (HCC). Astrocyte-elevated gene-1/Metadherin (AEG-1/MTDH) plays a key role in promoting MASH and HCC. AEG-1 is palmitoylated at residue cysteine 75 (Cys75) and a knock-in mouse representing mutated Cys75 to serine (AEG-1-C75S) showed activation of MASH- and HCC-promoting gene signature when compared to wild-type littermates (AEG-1-WT).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!