In Search of Zonation Markers to Identify Liver Functional Disorders

Yang, Qiuyuan; Zhang, Shuping; Ma, Juan; Liu, Sijin; Chen, Shuguang

doi:10.1155/2020/9374896

Cited by 7 publications

(8 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The finding suggested that tumor hepatocytes of HCC_P subtype presented a higher degree of urea cycle disorder (UCD), which correlated with poor prognosis 47 . Conversely, glycolysis was not a normal functional process of portal and periportal hepatocytes 23,49 , but we observed a slight upregulation of the glycolytic modules in tumor cells of HCC_P patients (Extended Data Fig. 6d).…”

Section: Intermediate State Analysis Reveals a Population Of Tumor Ce...mentioning

confidence: 76%

“…The hepatocytes have different states and functions along the CV to PV axis. The lobule can be roughly divided in four regions: central, middle, portal and peri-portal zones 5 (in a few studies the portal and peri-portal zones are combined as a single zone 23,24 ). We annotated hepatocyte zonation utilizing the gene signatures obtained from spatial transcriptomes (Methods, Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

uniLIVER: a Human Liver Cell Atlas for Data-Driven Cellular State Mapping

Wu,

Fan,

Miao

et al. 2023

Preprint

View full text Add to dashboard Cite

The liver performs several vital functions such as metabolism, toxin removal and glucose storage through the coordination of various cell types. The cell type compositions and cellular states undergo significant changes in abnormal conditions such as fatty liver, cirrhosis and liver cancer. As the recent breakthrough of the single-cell/single-nucleus RNA-seq (sc/snRNA-seq) techniques, there is a great opportunity to establish a reference cell map of liver at single cell resolution with transcriptome-wise features. In this study, we build a unified liver cell atlas uniLIVER by integrative analyzing a large-scale sc/snRNA-seq data collection of normal human liver with 331,125 cells and 79 samples from 6 datasets. Besides the hierarchical cell type annotations, uniLIVER also proposed a novel data-driven strategy to map any query dataset to the normal reference map by developing a machine learning based framework named LiverCT. Applying LiverCT on the datasets from multiple abnormal conditions (1,867,641 cells and 439 samples from 12 datasets), the alterations of cell type compositions and cellular states were systematically investigated in liver cancer.

show abstract

Section: Intermediate State Analysis Reveals a Population Of Tumor Ce...mentioning

confidence: 76%

Section: Resultsmentioning

confidence: 99%

uniLIVER: a Human Liver Cell Atlas for Data-Driven Cellular State Mapping

Wu,

Fan,

Miao

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…The liver architecture features a regular arrangement of hexagonal lobules, with each lobule containing periportal zone located at its corners, while the pericentral zone occupies the centre of the lobule. 8 Beyond its structural significance, the liver plays a crucial role as a central organ in governing iron metabolism. 9 Iron is imported into the liver mainly through the transferrin-transferrin receptor system, stored in the form of ferritin and exported by ferroportin (FPN).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Zonated iron deposition in the periportal zone of the liver is associated with selectively enhanced lipid synthesis

Yang,

Wu,

Liu

et al. 2023

Liver International

Self Cite

View full text Add to dashboard Cite

Background and AimsDisorders in liver lipid metabolism have been implicated in a range of metabolic conditions, including fatty liver and liver cancer. Altered lipid distribution within the liver, shifting from the pericentral to the periportal zone under pathological circumstances, has been observed; however, the underlying mechanism remains elusive. Iron, an essential metal, exhibits a zonal distribution in the liver similar to that of lipids. Nevertheless, the precise relationship between iron and lipid distribution, especially in the pericentral and periportal zones, remains poorly understood.MethodsWe conducted comprehensive in vitro and in vivo experiments, combining with in situ analysis and RNA sequencing, aiming for a detailed exploration of the causal relationship between iron accumulation and lipid metabolism.ResultsOur research suggests that iron overload can disrupt the normal distribution of lipids within the liver, particularly in the periportal zone. Through meticulous gene expression profiling in both the pericentral and periportal zones, we identified pyruvate carboxylase (PC) as a pivotal regulator in iron overload‐induced lipid accumulation. Additionally, we revealed that the activation of cyclic adenosine monophosphate response element binding protein (CREB) was indispensable for Pc gene expression when in response to iron overload.ConclusionsIn summary, our investigation unveils the crucial involvement of iron overload in fostering hepatic lipid accumulation in the periportal zone, at least partly mediated by the modulation of Pc expression. These insights offer new perspectives for understanding the pathogenesis of fatty liver diseases and their progression.

show abstract

“…The liver constitutes one of the largest organs of the body and exerts numerous essential functions associated with digestion, metabolism, protein synthesis and the detoxification of xenobiotics [1]. Hence, the liver is a primary site of various metabolic disorders [2]. Further, chronic hepatitis [3] and metabolic disorders [4] may result in liver fibrosis or even cirrhosis.…”

Section: Introductionmentioning

confidence: 99%

Liver Cell Type-Specific Targeting by Nanoformulations for Therapeutic Applications

Kaps,

Limeres,

Schneider

et al. 2023

IJMS

View full text Add to dashboard Cite

Hepatocytes exert pivotal roles in metabolism, protein synthesis and detoxification. Non-parenchymal liver cells (NPCs), largely comprising macrophages, dendritic cells, hepatic stellate cells and liver sinusoidal cells (LSECs), serve to induce immunological tolerance. Therefore, the liver is an important target for therapeutic approaches, in case of both (inflammatory) metabolic diseases and immunological disorders. This review aims to summarize current preclinical nanodrug-based approaches for the treatment of liver disorders. So far, nano-vaccines that aim to induce hepatitis virus-specific immune responses and nanoformulated adjuvants to overcome the default tolerogenic state of liver NPCs for the treatment of chronic hepatitis have been tested. Moreover, liver cancer may be treated using nanodrugs which specifically target and kill tumor cells. Alternatively, nanodrugs may target and reprogram or deplete immunosuppressive cells of the tumor microenvironment, such as tumor-associated macrophages. Here, combination therapies have been demonstrated to yield synergistic effects. In the case of autoimmune hepatitis and other inflammatory liver diseases, anti-inflammatory agents can be encapsulated into nanoparticles to dampen inflammatory processes specifically in the liver. Finally, the tolerance-promoting activity especially of LSECs has been exploited to induce antigen-specific tolerance for the treatment of allergic and autoimmune diseases.

show abstract

In Search of Zonation Markers to Identify Liver Functional Disorders

Cited by 7 publications

References 46 publications

uniLIVER: a Human Liver Cell Atlas for Data-Driven Cellular State Mapping

uniLIVER: a Human Liver Cell Atlas for Data-Driven Cellular State Mapping

Zonated iron deposition in the periportal zone of the liver is associated with selectively enhanced lipid synthesis

Liver Cell Type-Specific Targeting by Nanoformulations for Therapeutic Applications

Contact Info

Product

Resources

About