Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the mouse liver

AbstractReconstruction of heterogeneity through single cell transcriptional profiling has greatly advanced our understanding of the spatial liver transcriptome in recent years. However, global transcriptional differences across lobular units remain elusive in physical space. Here, we apply Spatial Transcriptomics to perform transcriptomic analysis across sectioned liver tissue. We confirm that the heterogeneity in this complex tissue is predominantly determined by lobular zonation. By introducing novel computational approaches, we enable transcriptional gradient measurements between tissue structures, including several lobules in a variety of orientations. Further, our data suggests the presence of previously transcriptionally uncharacterized structures within liver tissue, contributing to the overall spatial heterogeneity of the organ. This study demonstrates how comprehensive spatial transcriptomic technologies can be used to delineate extensive spatial gene expression patterns in the liver, indicating its future impact for studies of liver function, development and regeneration as well as its potential in pre-clinical and clinical pathology.

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Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the liver

10.1101/2021.01.11.426100 ◽

2021 ◽

Author(s):

Franziska Hildebrandt ◽

Alma Andersson ◽

Sami Saarenpää ◽

Ludvig Larsson ◽

Noémi Van Hul ◽

...

Keyword(s):

Liver Tissue ◽

Transcriptional Profiling ◽

Expression Patterns ◽

Physical Space ◽

Clinical Pathology ◽

Gene Expression Patterns ◽

Structural Components ◽

Computational Approaches ◽

Liver Transcriptome ◽

Gradient Measurements

ABSTRACTReconstruction of heterogeneity through single-cell transcriptional profiling has greatly advanced our understanding of the spatial liver transcriptome in recent years. However, global transcriptional differences across lobular units remain elusive in physical space. Here, we implement Spatial Transcriptomics to perform transcriptomic analysis across sectioned liver tissue. We confirm that the heterogeneity in this complex tissue is predominantly determined by lobular zonation. By introducing novel computational approaches, we enable transcriptional gradient measurements between tissue structures, including several lobules in a variety of orientations. Further, our data suggests the presence of previously transcriptionally uncharacterized structures within liver tissue, contributing to the overall spatial heterogeneity of the organ. This study demonstrates how comprehensive spatial transcriptomic technologies can be used to delineate extensive spatial gene expression patterns in the liver, indicating its future impact for studies of liver function, development and regeneration as well as its potential in pre-clinical and clinical pathology.

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THE MICRO-ANATOMY OF THE SMALLEST BILIARY PATHWAYS IN MOUSE LIVER TISSUE

Cells Tissues Organs ◽

10.1159/000141765 ◽

1961 ◽

Vol 46 (1-2) ◽

pp. 1-24 ◽

Cited By ~ 33

Author(s):

W.Th. Daems

Keyword(s):

Liver Tissue ◽

Mouse Liver ◽

Micro Anatomy

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Evidence that interaction of hepatocytes with the collecting (hepatic) veins triggers position-specific transcription of the glutamine synthetase and ornithine aminotransferase genes in the mouse liver

Molecular and Cellular Biology ◽

10.1128/mcb.11.12.6050-6058.1991 ◽

1991 ◽

Vol 11 (12) ◽

pp. 6050-6058

Author(s):

F C Kuo ◽

J E Darnell

Keyword(s):

Blood Flow ◽

Carbon Tetrachloride ◽

Glutamine Synthetase ◽

Liver Tissue ◽

Mouse Liver ◽

Hepatic Veins ◽

Surgical Removal ◽

Ornithine Aminotransferase ◽

Regenerating Liver ◽

Portal Veins

We previously demonstrated that glutamine synthetase (GS) and ornithine aminotransferase (OAT) mRNAs are expressed in the mouse liver acinus preferentially in pericentral hepatocytes, that is, those immediately surrounding terminal central veins (A.L. Bennett, K.E. Paulson, R.E. Miller, and J.E. Darnell, Jr., J. Cell Biol. 105:1073-1085, 1987, and F.C. Kuo, W.L. Hwu, D. Valle, and J.E. Darnell, Jr., Proc. Natl. Acad. Sci. USA, in press). We now show that hepatocytes surrounding large collecting hepatic veins but not portal veins also express these two mRNAs. The pericentral hepatocytes are the most distal hepatocytes with respect to acinar blood flow, whereas this is not necessarily the case for hepatocytes next to the large collecting hepatic veins. This result implies that it is contact with some hepatic venous element which signals positional expression. In an effort to induce conditions that change relationships between hepatocytes and blood vessels, regenerating liver was studied. After surgical removal of two-thirds or more of the liver, there was no noticeable change in GS or OAT expression in the remaining liver tissue during regeneration. However, treatment with carbon tetrachloride (CCl4), which specifically kills pericentral hepatocytes, completely removed GS- and OAT-containing cells and promptly halted hepatic transcription of GS. Repair of CCl4 damage is associated with invasion of inflammatory and scavenging cells, which remove dead hepatocytes to allow regrowth. Only when hepatocytes resumed contact with pericentral veins were the pretreatment levels of OAT and GS mRNA and high levels of GS transcription restored.

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CHANGES OF 8-OXO-2'-DEOXYGUANOSINE LEVEL IN MOUSE LIVER CELLS DNA IN CASE OF ACUTE TOXIC STRESS

Тонкие химические технологии ◽

10.32362/2410-6593-2016-11-6-68-74 ◽

2016 ◽

Vol 11 (6) ◽

pp. 68-74

Author(s):

N. V. Marmiy ◽

D. S. Esipov

Keyword(s):

Carbon Tetrachloride ◽

Liver Tissue ◽

Mouse Liver ◽

Pathological Change ◽

Liver Cells ◽

Antioxidant Systems ◽

Toxic Stress ◽

Laboratory Mice ◽

Short Term ◽

Initial Injection

The changes of the 8-oxo-2'-deoxyguanosine (8-oxo-dG)/dG ratio in the DNA of laboratory mice hepatocytes under the influence of toxic stress were studied. It was shown that the injection of carbon tetrachloride causes the growth of 8-oxo-dG level. A rapid increase in the level of 8-oxo-dG in DNA occurs during the first day of the experiment at short-term toxic stress. Subsequently, 48 hours after the initial injection, the level of 8-oxo-dG decreases to the control values. This change in the value of the biomarker can be attributed to the activation of the reparative and antioxidant systems. The subsequent injection results again in an increase of 8-oxo-dG level, and the latter only increases thereafter. This reflects the exhaustion of the reparative potential of the organism and accompanies the progress of inflammation and pathological change of the liver tissue.

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Sizing lipid droplets from adult and geriatric mouse liver tissue via nanoparticle tracking analysis

Analytical and Bioanalytical Chemistry ◽

10.1007/s00216-018-1016-8 ◽

2018 ◽

Vol 410 (16) ◽

pp. 3629-3638 ◽

Cited By ~ 2

Author(s):

Katherine A. Muratore ◽

Charles P. Najt ◽

Nicholas M. Livezey ◽

James Marti ◽

Douglas G. Mashek ◽

...

Keyword(s):

Liver Tissue ◽

Mouse Liver ◽

Lipid Droplets ◽

Nanoparticle Tracking Analysis

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Bubble-Induced Color Doppler Feedback Correlates with Histotripsy-Induced Destruction of Structural Components in Liver Tissue

Ultrasound in Medicine & Biology ◽

10.1016/j.ultrasmedbio.2017.11.012 ◽

2018 ◽

Vol 44 (3) ◽

pp. 602-612 ◽

Cited By ~ 4

Author(s):

Jonathan J. Macoskey ◽

Xi Zhang ◽

Timothy L. Hall ◽

Jiaqi Shi ◽

Shahaboddin Alahyari Beig ◽

...

Keyword(s):

Liver Tissue ◽

Color Doppler ◽

Structural Components

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Transcriptional Profiling of Polycythemia Vera Identifies Gene Expression Patterns Both Dependent and Independent from the Action of JAK2V617F

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-10-1092 ◽

2010 ◽

Vol 16 (17) ◽

pp. 4339-4352 ◽

Cited By ~ 23

Author(s):

Windy Berkofsky-Fessler ◽

Monica Buzzai ◽

Marianne K-H. Kim ◽

Steven Fruchtman ◽

Vesna Najfeld ◽

...

Keyword(s):

Gene Expression ◽

Polycythemia Vera ◽

Transcriptional Profiling ◽

Expression Patterns ◽

Gene Expression Patterns

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Transcriptional Profiling of Methyltransferase Genes during Growth of Methanosarcina mazei on Trimethylamine

Journal of Bacteriology ◽

10.1128/jb.00420-09 ◽

2009 ◽

Vol 191 (16) ◽

pp. 5108-5115 ◽

Cited By ~ 17

Author(s):

Christian Krätzer ◽

Paul Carini ◽

Raymond Hovey ◽

Uwe Deppenmeier

Keyword(s):

Transcriptional Profiling ◽

Expression Patterns ◽

Pcr Analysis ◽

Exponential Growth Phase ◽

Methane Formation ◽

Rt Pcr ◽

Transcript Levels ◽

Methanosarcina Mazei ◽

Depth Analysis ◽

Genes Encoding

ABSTRACT The genomic expression patterns of Methanosarcina mazei growing with trimethylamine were measured in comparison to those of cells grown with methanol. We identified a total of 72 genes with either an increased level (49 genes) or a decreased level (23 genes) of mRNA during growth on trimethylamine with methanol-grown cells as the control. Major differences in transcript levels were observed for the mta, mtb, mtt, and mtm genes, which encode enzymes involved in methane formation from methanol and trimethylamine, respectively. Other differences in mRNA abundance were found for genes encoding enzymes involved in isopentenyl pyrophosphate synthesis and in the formation of aromatic amino acids, as well as a number of proteins with unknown functions. The results were verified by in-depth analysis of methyltransferase genes using specific primers for real-time quantitative reverse transcription-PCR (RT-PCR). The monitored transcript levels of genes encoding corrinoid proteins involved in methyl group transfer from methylated C1 compounds (mtaC, mtbC, mttC, and mtmC) indicated increased amounts of mRNA from the mtaBC1, mtaBC2, and mtaBC3 operons in methanol-grown cells, whereas mRNA of the mtb1-mtt1 operon was found in high concentrations during trimethylamine consumption. The genes of the mtb1-mtt1 operon encode methyltransferases that are responsible for sequential demethylation of trimethylamine. The analysis of product formation of trimethylamine-grown cells at different optical densities revealed that large amounts of dimethylamine and monomethylamine were excreted into the medium. The intermediate compounds were consumed only in the very late exponential growth phase. RT-PCR analysis of key genes involved in methanogenesis led to the conclusion that M. mazei is able to adapt to changing trimethylamine concentrations and the consumption of intermediate compounds. Hence, we assume that the organism possesses a regulatory network for optimal substrate utilization.

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Development of an Ion-Pair Reverse-Phase Liquid Chromatographic/Tandem Mass Spectrometry Method for the Determination of an 18-Mer Phosphorothioate Oligonucleotide in Mouse Liver Tissue

European Journal of Mass Spectrometry ◽

10.1255/ejms.674 ◽

2005 ◽

Vol 11 (2) ◽

pp. 209-215 ◽

Cited By ~ 22

Author(s):

Anthony T. Murphy ◽

Patricia Brown-Augsburger ◽

Rosie Z. Yu ◽

Richard S. Geary ◽

Stefan Thibodeaux ◽

...

Keyword(s):

Mass Spectrometry ◽

Tandem Mass Spectrometry ◽

Liver Tissue ◽

Mouse Liver ◽

Ion Pair ◽

Tandem Mass ◽

Phosphorothioate Oligonucleotide ◽

Reverse Phase ◽

Discovery Research

A quantitative method for the determination of a partially modified, 2′-ribose alkoxy 18-mer phosphorothioate oligonucleotide in liver tissue has been developed. A liquid:liquid extraction, ion-pair reverse phase chromatographic separation and tandem mass spectrometry were used to achieve a quantitation range of 125 to 10,000 ng g−1 mouse liver tissue. A total cycle time of 5 min was obtained while maintaining separation of three potential impurities. Separations were performed using a Discovery RP-Amide C16, 100 × 2 mm column packed with 5 μm particles. The separation was facilitated by the use of triethylamine (TEA) and hexafluoroisopropanol (HFIP) as ion-pair agents. The method has subsequently been used for the determination of other phosphorothioate oligonucleotides in support of discovery research.

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