Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Liver zonation, essential for diverse physiological functions, is lacking in existing organoid models, hindering their ability to recapitulate liver development and pathogenesis. Addressing this gap, this work explores the feasibility of achieving zonated organoid by co-culturing human embryonic stem cells (hESCs) derived hepatocytes (HEP) with hESCs derived liver sinusoidal endothelial cells (LSECs) exhibiting characteristics of either the liver lobule's pericentral (PC) or periportal (PP) regions. Introducing zonated LSECs with variable WNT2 signaling subtly regulate hepatocyte zonation, resulting in noticeable metabolic function changes. Considering the lipid metabolism variations in PC and PP organoids, this work constructs biomimetic zonated metabolic dysfunction-associated steatotic liver disease (MASLD) organoids and revealed that glucagon-like peptide-1 receptor agonist (GLP-1RA) directly target LSECs, indicating potential therapeutic mechanisms of GLP-1RA in MAFLD alleviation. This study highlights the crucial role of non-parenchymal cells in organoids for recapitulating niche heterogeneity, offering further insights for drug discovery and in vitro modeling of organ heterogeneity.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12120767 | PMC |
| http://dx.doi.org/10.1002/advs.202411667 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Visualization of CYP3A4 expression at both mRNA and protein levels simultaneously at single cell resolution in various conditions using RNAscope combined with immunofluorescence.
Drug Metab Dispos
July 2025
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut. Electronic address:
Precise characterization of drug-metabolizing enzyme expression, such as CYP3A4, at the single-cell resolution is essential for understanding hepatic functional heterogeneity and its impact on xenobiotic clearance. In this study, we employed RNAscope in situ hybridization combined with immunofluorescence to simultaneously visualize CYP3A4 mRNA and protein expression in individual cells under diverse experimental conditions. Using differentiated HepaRG cells, we identified distinct CYP3A4-positive and CYP3A4-negative subpopulations in metabolic zonation.
View Article and Find Full Text PDFSex-Related Variations in Liver Homeostasis and Disease: From Zonation Dynamics to Clinical Implications.
J Hepatol
August 2025
Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, P.O. Box 3000, 90014, Oulu, Finland.
The liver exhibits pronounced sexual dimorphism, characterised by sex-specific differences in structure, metabolic function, and susceptibility to disease. Although traditionally considered homogeneous, the liver exhibits significant zonal heterogeneity, with periportal and pericentral regions differing considerably in terms of oxygen availability, metabolic activity and partially cell composition. In recent years, new technologies such as single-cell RNA sequencing and spatial proteomics have revealed numerous sex-specific differences in gene and protein expression that align with the spatial heterogeneity of liver functions.
View Article and Find Full Text PDFEndothelial c-Maf prevents MASLD-like liver fibrosis by regulating chromatin accessibility to suppress pathogenic microvascular cell subsets.
JHEP Rep
September 2025
Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, Mannheim, Germany.
Background & Aims: Liver sinusoidal endothelial cells (LSECs) are highly specialized components of the hepatic vascular niche, regulating liver function and disease pathogenesis through angiocrine signaling. Recently, we identified GATA4 as a key transcription factor controlling LSEC development and protecting against liver fibrosis. As the transcription factor c-Maf was strongly downregulated in -deficient LSECs, we hypothesized that c-Maf might be an important downstream effector of GATA4 in LSEC differentiation and liver fibrogenesis.
View Article and Find Full Text PDFCurrent Advances and Future Perspectives of Liver-on-a-Chip Platforms Incorporating Dynamic Fluid Flow.
Biomimetics (Basel)
July 2025
Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of Korea.
The liver is a vital organ responsible for a broad range of metabolic functions, including glucose and lipid metabolism, detoxification, and protein synthesis. Its structural complexity, characterized by hexagonal hepatic lobules composed of diverse parenchymal and non-parenchymal cell types, supports its broad spectrum of physiological activities. Traditional in vitro liver models have contributed significantly to our understanding of hepatic biology and the development of therapies for liver-related diseases.
View Article and Find Full Text PDF