A Single‐Cell Perspective of the Mammalian Liver in Health and Disease

Xiong, Xuelian; Kuang, Henry; Liu, Tongyu; Lin, Jiandie D.

doi:10.1002/hep.31149

Cited by 30 publications

(29 citation statements)

References 33 publications

(75 reference statements)

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“…Single-cell RNA sequencing and single-nucleus RNA sequencing allowed scientists to characterize transcriptomes of individual cells in human and rodent liver, to establish a cell-atlas of the human liver, and to understand the functions and crosstalk of hepatic cell types [ 73 ]. Though most evidence is from murine models, and study normal liver, liver cancer, or cirrhosis, transcriptomic studies of liver biopsies from NAFLD patients have already offered a number of promising biomarkers [ 74 ].…”

Section: Single-cell and Cell Type-resolved Omics Approaches To Namentioning

confidence: 99%

The Role of Diagnostic Biomarkers, Omics Strategies, and Single-Cell Sequencing for Nonalcoholic Fatty Liver Disease in Severely Obese Patients

Wernberg

Ravnskjær

Lauridsen

et al. 2021

JCM

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Liver disease due to metabolic dysfunction constitute a worldwide growing health issue. Severe obesity is a particularly strong risk factor for non-alcoholic fatty liver disease, which affects up to 93% of these patients. Current diagnostic markers focus on the detection of advanced fibrosis as the major predictor of liver-related morbidity and mortality. The most accurate diagnostic tools use elastography to measure liver stiffness, with diagnostic accuracies similar in normal-weight and severely obese patients. The effectiveness of elastography tools are however hampered by limitations to equipment and measurement quality in patients with very large abdominal circumference and subcutaneous fat. Blood-based biomarkers are therefore attractive, but those available to date have only moderate diagnostic accuracy. Ongoing technological advances in omics technologies such as genomics, transcriptomics, and proteomics hold great promise for discovery of biomarkers and increased pathophysiological understanding of non-alcoholic liver disease and steatohepatitis. Very recent developments have allowed for single-cell sequencing and cell-type resolution of gene expression and function. In the near future, we will therefore likely see a multitude of breakthrough biomarkers, developed from a deepened understanding of the biological function of individual cell types in the healthy and injured liver.

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Section: Single-cell and Cell Type-resolved Omics Approaches To Namentioning

confidence: 99%

The Role of Diagnostic Biomarkers, Omics Strategies, and Single-Cell Sequencing for Nonalcoholic Fatty Liver Disease in Severely Obese Patients

Wernberg

Ravnskjær

Lauridsen

et al. 2021

JCM

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“…Moreover, pericentral regions are more specialized in antioxidative stress and detoxification activities, carried out by glutamine synthetase (GS) and cytochrome P450 (CYP450) enzymes, as well as glycolysis, lipogenesis, and bile acid synthesis. Periportal regions undertake several energy-consuming processes, including cholesterol (CHO) synthesis, urea synthesis, gluconeogenesis, and fatty acid oxidation, and exhibit the highest level of albumin expression ( Figure 3 ) ( Table 1 ) [ 13 , 14 ].…”

Section: Current Markers Used To Identify Liver Zonationmentioning

confidence: 99%

“…NAFLD, which is present in 25% of the world's population, starts with the uncontrolled accumulation of fat in hepatocytes, causing inflammation and fibrosis in the liver [ 25 ]. In NAFLD patients, hepatic steatosis is obvious in pericentral hepatocytes [ 14 ]. A high-fat diet was found to induce the deposition of triglycerides (TGs) in areas surrounding the periportal zones in NAFLD animal models, suggesting that TGs might be a marker to identify NAFLD ( Table 3 ) [ 26 ].…”

Section: Disordered Liver Zonation Points To Abnormal Metabolism Amentioning

confidence: 99%

“…Although some biomarkers and genes have been reported as markers for identifying liver zonation in both normal and pathological states, issues in the early detection of liver disorders have not been addressed. To overcome the technical challenges, some emerging strategies and techniques, such as single-cell RNA sequencing (scRNA-seq), are being employed to shed light on the heterogeneity of hepatocytes and disease-related cellular reprogramming [ 14 ]. In combination with single-molecule fluorescence in situ hybridization, scRNA-seq can generate a high-resolution visual map of RNA expression in spatial and global dimensions of the liver, making it feasible to explore more accurate zonation markers in the future [ 39 ].…”

Section: Continued Efforts In Search Of New Zonation Markersmentioning

confidence: 99%

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In Search of Zonation Markers to Identify Liver Functional Disorders

Yang

Zhang

et al. 2020

Oxidative Medicine and Cellular Longevity

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A substantial amount of research is being conducted on zonation markers to identify hepatic injuries and disorders based on the structural and functional zonation of the liver. In contrast to metabolic zonation, hepatocyte ploidy reflects the capability of liver regenerative turnover. Nonetheless, many knowledge gaps remain in the understanding of the links between liver disorders and altered zonation and ploidy, partially owing to the lack of sufficient zonation markers. Under this setting, we recapitulated the currently known and prospective markers used to identify normal and altered liver zonation in different disorders. Furthermore, we discussed new findings from studies that have used advanced methodologies to identify potential markers with greater accuracy. We also elaborated on the perspectives and future applications of zonation research in the early detection of various liver diseases.

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“…In addition, investigation of scRNA-seq of human liver cells has revealed remarkably conserved features of liver zonation between mouse and human, i.e. the spatial separation of the immense spectrum of different metabolic pathways along the liver sinusoids between mouse and human [21,22]. Furthermore, we use CRC mapper to identify the core transcription factors in each species (Figure 8).…”

Section: Function Comparison Across Speciesmentioning

confidence: 99%

Comparative Analysis of Super-enhancers Across Mammals Reveals Their High Function Conservation

Peng¹,

Zhang²

2020

Preprint

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BackgroundSuper-enhancers (SEs) are key positive regulatory elements in defining cells/tissues identity in mammals, yet their similarities and differences of sequence and function across mammals have been poor studied. To allow sequence and function comparison across mammalian SEs, we employ H3K27ac ChIP-seq data to six cell types/tissues across human, pig, and mouse, which represent different lineages of mammals in the evolutionary tree.ResultsOverall, a median of 848 human SEs, 888 pig SEs and 503 mouse SEs are identified across cells/tissues. These SEs are largely distributed in promoter regions for human (91.9% in median) and mouse (63.4% in median), while mostly in distal intergenic regions for pig (66.1% in median). Extremely higher unique orthologous SEs frequency (91.6%~92.1%) has been detected for the same cell/tissue across species. Consistently, their overlapping rates are very low for the same cell/tissue across species (0.1%~0.5%). For the SE-associated orthologous genes, they also show high unique frequency for species (63.3%~83.9%) and low overlapping rates (0.8%~1.3%) at inter-species comparison. However, orthologous SEs function comparisons across species have shown similar biological processes related to cells/tissues identity in the top 15 significant enriched terms for the same cell/tissue. Meanwhile, common core transcription factors that determine cells/tissues identity are determined for the same cell/tissue across mammals.ConclusionsThis study highlights the differences of SEs genomic distribution across mammals. It reveals low orthologous sequence overlapping but high function conservation of SEs across mammals. It would improve our understanding of regulation function cis-regulatory elements in mammals.

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A Single‐Cell Perspective of the Mammalian Liver in Health and Disease

Cited by 30 publications

References 33 publications

The Role of Diagnostic Biomarkers, Omics Strategies, and Single-Cell Sequencing for Nonalcoholic Fatty Liver Disease in Severely Obese Patients

The Role of Diagnostic Biomarkers, Omics Strategies, and Single-Cell Sequencing for Nonalcoholic Fatty Liver Disease in Severely Obese Patients

In Search of Zonation Markers to Identify Liver Functional Disorders

Comparative Analysis of Super-enhancers Across Mammals Reveals Their High Function Conservation

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