scholarly journals Molecular characterization and cell type composition deconvolution of fibrosis in NAFLD

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lorena Pantano ◽  
George Agyapong ◽  
Yang Shen ◽  
Zhu Zhuo ◽  
Francesc Fernandez-Albert ◽  
...  
Keyword(s):  
Liver Disease ◽  
Molecular Mechanisms ◽  
Fibrosis Stage ◽  
Cell Type ◽  
Full Spectrum ◽  
Alcoholic Fatty Liver ◽  
Cell Type Composition ◽  
Type Composition ◽  
Stage 4 ◽  
Apoptotic Pathways

AbstractNon-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. In adults with NAFLD, fibrosis can develop and progress to liver cirrhosis and liver failure. However, the underlying molecular mechanisms of fibrosis progression are not fully understood. Using total RNA-Seq, we investigated the molecular mechanisms of NAFLD and fibrosis. We sequenced liver tissue from 143 adults across the full spectrum of fibrosis stage including those with stage 4 fibrosis (cirrhosis). We identified gene expression clusters that strongly correlate with fibrosis stage including four genes that have been found consistently across previously published transcriptomic studies on NASH i.e. COL1A2, EFEMP2, FBLN5 and THBS2. Using cell type deconvolution, we estimated the loss of hepatocytes versus gain of hepatic stellate cells, macrophages and cholangiocytes with advancing fibrosis stage. Hepatocyte-specific functional analysis indicated increase of pro-apoptotic pathways and markers of bipotent hepatocyte/cholangiocyte precursors. Regression modelling was used to derive predictors of fibrosis stage. This study elucidated molecular and cell composition changes associated with increasing fibrosis stage in NAFLD and defined informative gene signatures for the disease.

scholarly journals Cell Type Aware analysis of RNA-seq data (CARseq) reveals difference and similarities of the molecular mechanisms of Schizophrenia and Autism

2020 ◽  
Author(s):  
Chong Jin ◽  
Mengjie Chen ◽  
Danyu Lin ◽  
Wei Sun
Keyword(s):  
Differential Expression ◽  
Molecular Mechanisms ◽  
Differential Expression Analysis ◽  
Cell Types ◽  
Cell Type ◽  
Specific Expression ◽  
Tissue Samples ◽  
Cell Type Composition ◽  
Type Composition ◽  
Cell Type Specific Expression

AbstractMost tissue samples are composed of different cell types. Differential expression analysis without accounting for cell type composition cannot separate the changes due to cell type composition or cell type-specific expression. We propose a new framework to address these limitations: Cell Type Aware analysis of RNA-seq (CARseq). After evaluating its performance in simulations, we apply CARseq to compare gene expression of schizophrenia/autism subjects versus controls. Our results show that these two neurodevelopmental disorders differ from each other in terms of cell type composition changes and differential expression associated with different types of neurotransmitter receptors. We also discover overlapping signals of differential expression in microglia, supporting the two diseases’ similarity through immune regulation.

scholarly journals Adjustment of Cell-Type Composition Minimizes Systematic Bias in Blood DNA Methylation Profiles Derived by DNA Collection Protocols

PLoS ONE ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. e0147519 ◽  
Author(s):  
Yuh Shiwa ◽  
Tsuyoshi Hachiya ◽  
Ryohei Furukawa ◽  
Hideki Ohmomo ◽  
Kanako Ono ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Systematic Bias ◽  
Cell Type ◽  
Cell Type Composition ◽  
Type Composition ◽  
Dna Collection

Molecular mechanisms of non-alcoholic fatty liver disease development

2021 ◽  
Vol 24 (4) ◽  
pp. 120
Author(s):  
T.S. Sall ◽  
E.S. Shcherbakova ◽  
S.I. Sitkin ◽  
T.Ya. Vakhitov ◽  
I.G. Bakulin ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Disease Development ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals Seasonal changes in gene expression represent cell-type composition in whole blood

2014 ◽  
Vol 23 (10) ◽  
pp. 2721-2728 ◽  
Author(s):  
S. De Jong ◽  
M. Neeleman ◽  
J. J. Luykx ◽  
M. J. Ten Berg ◽  
E. Strengman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Whole Blood ◽  
Seasonal Changes ◽  
Cell Type ◽  
Cell Type Composition ◽  
Type Composition

scholarly journals Assessing the Contribution of Relative Macrophage Frequencies to Subcutaneous Adipose Tissue

2021 ◽  
Vol 8 ◽  
Author(s):  
Marianthi Kalafati ◽  
Michael Lenz ◽  
Gökhan Ertaylan ◽  
Ilja C. W. Arts ◽  
Chris T. Evelo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Tissue Cell ◽  
Cell Type ◽  
Expression Of Genes ◽  
Cell Type Composition ◽  
Type Composition ◽  
Adipose Tissue Cell ◽  
Subcutaneous Adipose

Background: Macrophages play an important role in regulating adipose tissue function, while their frequencies in adipose tissue vary between individuals. Adipose tissue infiltration by high frequencies of macrophages has been linked to changes in adipokine levels and low-grade inflammation, frequently associated with the progression of obesity. The objective of this project was to assess the contribution of relative macrophage frequencies to the overall subcutaneous adipose tissue gene expression using publicly available datasets.Methods: Seven publicly available microarray gene expression datasets from human subcutaneous adipose tissue biopsies (n = 519) were used together with TissueDecoder to determine the adipose tissue cell-type composition of each sample. We divided the subjects in four groups based on their relative macrophage frequencies. Differential gene expression analysis between the high and low relative macrophage frequencies groups was performed, adjusting for sex and study. Finally, biological processes were identified using pathway enrichment and network analysis.Results: We observed lower frequencies of adipocytes and higher frequencies of adipose stem cells in individuals characterized by high macrophage frequencies. We additionally studied whether, within subcutaneous adipose tissue, interindividual differences in the relative frequencies of macrophages were reflected in transcriptional differences in metabolic and inflammatory pathways. Adipose tissue of individuals with high macrophage frequencies had a higher expression of genes involved in complement activation, chemotaxis, focal adhesion, and oxidative stress. Similarly, we observed a lower expression of genes involved in lipid metabolism, fatty acid synthesis, and oxidation and mitochondrial respiration.Conclusion: We present an approach that combines publicly available subcutaneous adipose tissue gene expression datasets with a deconvolution algorithm to calculate subcutaneous adipose tissue cell-type composition. The results showed the expected increased inflammation gene expression profile accompanied by decreased gene expression in pathways related to lipid metabolism and mitochondrial respiration in subcutaneous adipose tissue in individuals characterized by high macrophage frequencies. This approach demonstrates the hidden strength of reusing publicly available data to gain cell-type-specific insights into adipose tissue function.

Is liver fat detrimental to vessels?: intersections in the pathogenesis of NAFLD and atherosclerosis

2008 ◽  
Vol 115 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Paola Loria ◽  
Amedeo Lonardo ◽  
Giovanni Targher
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Liver Fat ◽  
Cvd Risk ◽  
Alcoholic Fatty Liver ◽  
Insulin Resistant ◽  
Major Player

NAFLD (non-alcoholic fatty liver disease) encompasses the spectrum of fatty liver disease in insulin-resistant individuals who often display T2DM (Type 2 diabetes mellitus) and obesity. The present review highlights the pathophysiological basis and clinical evidence for a possible causal linkage between NAFLD and CVD (cardiovascular disease). The role of traditional and non-traditional CVD risk factors in the pathophysiology of NAFLD is considered in the first part of the review, with the basic science shared by atherogenesis and hepatic steatogenesis discussed in depth in the second part. In conclusion, NAFLD is not an innocent bystander, but a major player in the development and progression of CVD. NAFLD and CVD also share similar molecular mechanisms and targeted treatment strategies. On the research side, studies should focus on interventions aimed at restoring energy homoeostasis in lipotoxic tissues and at improving hepatic (micro)vascular blood supply.

scholarly journals Single nuclei sequencing of entire mammalian hearts: strain-dependent cell-type composition and velocity

2020 ◽  
Vol 116 (7) ◽  
pp. 1249-1251
Author(s):  
Markus Wolfien ◽  
Anne-Marie Galow ◽  
Paula Müller ◽  
Madeleine Bartsch ◽  
Ronald M Brunner ◽  
...  
Keyword(s):  
Cell Type ◽  
Cell Type Composition ◽  
Type Composition ◽  
Dependent Cell ◽  
Strain Dependent

scholarly journals A Role for Gut Microbiome Fermentative Pathways in Fatty Liver Disease Progression

2020 ◽  
Vol 9 (5) ◽  
pp. 1369 ◽  
Author(s):  
Paula Iruzubieta ◽  
Juan M. Medina ◽  
Raúl Fernández-López ◽  
Javier Crespo ◽  
Fernando de la Cruz
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Disease Progression ◽  
Gut Microbiome ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Alcohol Fermentation ◽  
Alcoholic Fatty Liver ◽  
Liver Disease Progression ◽  
The Impact

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease in which environmental and genetic factors are involved. Although the molecular mechanisms involved in NAFLD onset and progression are not completely understood, the gut microbiome (GM) is thought to play a key role in the process, influencing multiple physiological functions. GM alterations in diversity and composition directly impact disease states with an inflammatory course, such as non-alcoholic steatohepatitis (NASH). However, how the GM influences liver disease susceptibility is largely unknown. Similarly, the impact of strategies targeting the GM for the treatment of NASH remains to be evaluated. This review provides a broad insight into the role of gut microbiota in NASH pathogenesis, as a diagnostic tool, and as a therapeutic target in this liver disease. We highlight the idea that the balance in metabolic fermentations can be key in maintaining liver homeostasis. We propose that an overabundance of alcohol-fermentation pathways in the GM may outcompete healthier, acid-producing members of the microbiota. In this way, GM ecology may precipitate a self-sustaining vicious cycle, boosting liver disease progression.

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