scholarly journals Mouse lipidomics reveals inherent flexibility of a mammalian lipidome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michał A. Surma ◽  
Mathias J. Gerl ◽  
Ronny Herzog ◽  
Jussi Helppi ◽  
Kai Simons ◽  
...  
Keyword(s):  
Quantitative Assessment ◽  
Pharmaceutical Research ◽  
Cell Types ◽  
Model Organisms ◽  
Murine Models ◽  
Systematic Analysis ◽  
Bodily Fluids ◽  
Mouse Tissues ◽  
Organ Specific ◽  
Different Cell Types

AbstractLipidomics has become an indispensable method for the quantitative assessment of lipid metabolism in basic, clinical, and pharmaceutical research. It allows for the generation of information-dense datasets in a large variety of experimental setups and model organisms. Previous studies, mostly conducted in mice (Mus musculus), have shown a remarkable specificity of the lipid compositions of different cell types, tissues, and organs. However, a systematic analysis of the overall variation of the mouse lipidome is lacking. To fill this gap, in the present study, the effect of diet, sex, and genotype on the lipidomes of mouse tissues, organs, and bodily fluids has been investigated. Baseline quantitative lipidomes consisting of 796 individual lipid molecules belonging to 24 lipid classes are provided for 10 different sample types. Furthermore, the susceptibility of lipidomes to the tested parameters is assessed, providing insights into the organ-specific lipidomic plasticity and flexibility. This dataset provides a valuable resource for basic and pharmaceutical researchers working with murine models and complements existing proteomic and transcriptomic datasets. It will inform experimental design and facilitate interpretation of lipidomic datasets.

scholarly journals Flexibility of a mammalian lipidome - insights from mouse lipidomics

2021 ◽  
Author(s):  
Michal A. Surma ◽  
Mathias J. Gerl ◽  
Ronny Herzog ◽  
Jussi Helppi ◽  
Kai Simons ◽  
...  
Keyword(s):  
Quantitative Assessment ◽  
Pharmaceutical Research ◽  
Cell Types ◽  
Model Organisms ◽  
Murine Models ◽  
Systematic Analysis ◽  
Bodily Fluids ◽  
Mouse Tissues ◽  
Organ Specific ◽  
Different Cell Types

Lipidomics has become an indispensable method for the quantitative assessment of lipid metabolism in basic, clinical, and pharmaceutical research. It allows for the generation of information-dense datasets in a large variety of experimental setups and model organisms. Previous studies, mostly conducted in mice (Mus musculus), have shown a remarkable specificity of the lipid compositions of different cell types, tissues, and organs. However, a systematic analysis of the overall variation of the mouse lipidome is lacking. To fill this gap, in the present study, the effect of diet, sex, and genotype on the lipidomes of mouse tissues, organs, and bodily fluids has been investigated. Baseline quantitative lipidomes consisting of 796 individual lipid molecules belonging to 24 lipid classes are provided for 10 different sample types. Furthermore, the susceptibility of lipidomes to the tested parameters is assessed, providing insights into the organ-specific lipidomic plasticity and flexibility. This dataset provides a valuable resource for basic and pharmaceutical researchers working with murine models and complements existing proteomic and transcriptomic datasets. It will inform experimental design and facilitate interpretation of lipidomic datasets.

Parenteral vs. oral iron: influence on hepcidin signaling pathways through analysis of Hfe/Tfr2-null mice

2014 ◽  
Vol 306 (2) ◽  
pp. G132-G139 ◽  
Author(s):  
Cameron J. McDonald ◽  
Daniel F. Wallace ◽  
Lesa Ostini ◽  
V. Nathan Subramaniam
Keyword(s):  
Iron Homeostasis ◽  
Regulatory System ◽  
Cell Types ◽  
Deficiency Anemia ◽  
Systematic Analysis ◽  
Cellular Iron ◽  
Morphogenetic Protein ◽  
Smad Signaling Pathway ◽  
Associated Proteins ◽  
Different Cell Types

Treatment for iron deficiency anemia can involve iron supplementation via dietary or parenteral routes that result in different cellular iron distributions. The effect of the administered iron on the iron regulatory system and hepcidin in the liver has not been well studied. Hepcidin, the liver-expressed central iron-regulatory peptide, is itself regulated through the bone morphogenetic protein (BMP)/SMAD signaling pathway. Specifically, Bmp6 expression is upregulated in response to iron and induces hepcidin through phosphorylation of Smad1/5/8. The hemochromatosis-associated proteins Hfe and transferrin receptor 2 (Tfr2) are known upstream regulators of hepcidin, although their precise roles are still unclear. To investigate the mechanisms of this regulation and the roles of the Hfe and Tfr2, we subjected wild-type, Hfe−/−, Tfr2−/−, and Hfe−/−/ Tfr2−/− mice to iron loading via dietary or parenteral routes. Systematic analysis demonstrated that Tfr2 is required for effective upregulation of Bmp6 in response to hepatocyte iron, but not nonparenchymal iron. Hfe is not required for Bmp6 upregulation, regardless of iron localization, but rather, is required for efficient downstream transmission of the regulatory signal. Our results demonstrate that Hfe and Tfr2 play separate roles in the regulatory responses to iron compartmentalized in different cell types and further elucidates the regulatory mechanisms controlling iron homeostasis.

scholarly journals Joint reconstruction of cis-regulatory interaction networks across multiple tissues using single-cell chromatin accessibility data

2020 ◽  
Author(s):  
Kangning Dong ◽  
Shihua Zhang
Keyword(s):  
Single Cell ◽  
Regulatory Networks ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Computational Method ◽  
Regulatory Mechanisms ◽  
Regulatory Interaction ◽  
Regulatory Interactions ◽  
Mouse Tissues ◽  
Different Cell Types

Abstract The rapid accumulation of single-cell chromatin accessibility data offers a unique opportunity to investigate common and specific regulatory mechanisms across different cell types. However, existing methods for cis-regulatory network reconstruction using single-cell chromatin accessibility data were only designed for cells belonging to one cell type, and resulting networks may be incomparable directly due to diverse cell numbers of different cell types. Here, we adopt a computational method to jointly reconstruct cis-regulatory interaction maps (JRIM) of multiple cell populations based on patterns of co-accessibility in single-cell data. We applied JRIM to explore common and specific regulatory interactions across multiple tissues from single-cell ATAC-seq dataset containing ~80 000 cells across 13 mouse tissues. Reconstructed common interactions among 13 tissues indeed relate to basic biological functions, and individual cis-regulatory networks show strong tissue specificity and functional relevance. More importantly, tissue-specific regulatory interactions are mediated by coordination of histone modifications and tissue-related TFs, and many of them may reveal novel regulatory mechanisms.

scholarly journals Joint reconstruction of cis-regulatory interaction networks across multiple tissues using single-cell chromatin accessibility data

2019 ◽  
Author(s):  
Kangning Dong ◽  
Shihua Zhang
Keyword(s):  
Single Cell ◽  
Regulatory Network ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Computational Method ◽  
Regulatory Mechanisms ◽  
Regulatory Interactions ◽  
Mouse Tissues ◽  
Functional Relevance ◽  
Different Cell Types

ABSTRACTThe rapid accumulation of single-cell chromatin accessibility data offers a unique opportunity to investigate common and specific regulatory mechanisms across different cell types. However, existing methods for cis-regulatory network reconstruction using single-cell chromatin accessibility data were only designed for cells belonging to one cell type, and resulting networks may be incomparable directly due to diverse cell numbers of different cell types. Here, we adopt a computational method to jointly reconstruct cis-regulatory interaction maps (JRIM) of multiple cell populations based on patterns of co-accessibility in single-cell data. We applied JRIM to explore common and specific regulatory interactions across multiple tissues from single-cell ATAC-seq dataset containing ~80,000 cells across 13 mouse tissues. Reconstructed common interactions among 13 tissues indeed relate to basic biological functions, and individual cis-regulatory network shows strong tissue specificity and functional relevance. More importantly, tissue-specific regulatory interactions are mediated by coordination of histone modifications and tissue related TFs, and many of them reveal novel regulatory mechanisms (e.g., a kidney-specific promoter-enhancer loop of clock-controlled gene Gys2).

scholarly journals Evaluation of the antifibrotic potency by knocking down SPARC, CCR2 and SMAD3

2018 ◽  
Author(s):  
Weifeng Ding ◽  
Weilin Pu ◽  
Shuai Jiang ◽  
Yanyun Ma ◽  
Qingmei Liu ◽  
...  
Keyword(s):  
Inflammatory Cells ◽  
Cell Types ◽  
Biological Pathways ◽  
Triple Combination ◽  
Aberrant Expression ◽  
Mouse Tissues ◽  
Peptide Nanoparticles ◽  
Fibrotic Disorders ◽  
Combination Of Sirnas ◽  
Different Cell Types

AbstractThe genes of SPARC, CCR2, and SMAD3 are implicated in orchestrating inflammation and fibrosis in scleroderma and other fibrotic disorders. Aim of the studies was to examine synergistic effect of inhibition of these genes in treating fibrosis. The peptide nanoparticles were used to deliver the siRNAs in bleomycin-induced fibrotic mice. Triple combination of siRNAs targeting on Sparc, Ccr2 and Smad3 achieved favorable anti-inflammatory and anti-fibrotic effects. Inhibition of inflammation was evidenced by reduced inflammatory cells and proinflammatory cytokines in the BALF and/or the tissues. Activation of fibroblasts was suppressed in mouse tissues in which α-Sma and collagens were significantly reduced. Aberrant expression of the genes in fibroblasts, monocytes/macrophage, endothelial and epithelial cells were reinstalled after the treatment. In addition, transcriptome profiles indicated that some bleomycin-induced alterations of multiple biological pathways were recovered to varying degrees by the treatment. The results indicated that the triple combination of siRNAs systemically reinstated multiple biopathways, probably through controlling on different cell types including fibroblasts, monocytes/macrophages, endothelial cells and others. The multi-target-combined therapeutic approach examined herein may represent a novel and effective therapy for fibrosis.

scholarly journals Mapping biology from mouse to man using transfer learning

2019 ◽  
Author(s):  
Patrick S. Stumpf ◽  
Doris Du ◽  
Haruka Imanishi ◽  
Yuya Kunisaki ◽  
Yuichiro Semba ◽  
...  
Keyword(s):  
Machine Learning ◽  
Transfer Learning ◽  
Biomedical Research ◽  
Human Cell ◽  
Cell Types ◽  
Human Cells ◽  
Model Organisms ◽  
Using Data ◽  
Artificial Neural Network Ann ◽  
Different Cell Types

Biomedical research often involves conducting experiments on model organisms in the anticipation that the biology learnt from these experiments will transfer to the human. Yet, it is commonly the case that biology does not transfer effectively, often for unknown reasons. Despite its importance to translational research this transfer process is not currently rigorously quantified. Here, we show that transfer learning – the branch of machine learning that concerns passing information from one domain to another – can be used to efficiently map biology from mouse to man, using the bone marrow (BM) as a representative example of a complex tissue. We first trained an artificial neural network (ANN) to accurately recognize various different cell types in mouse BM using data obtained from single-cell RNA-sequencing (scRNA-Seq) experiments. We found that this ANN, trained exclusively on mouse data, was able to identify individual human cells obtained from comparable scRNA-Seq experiments of human BM with 83% overall accuracy. However, while some human cell types were easily identified, others were not, indicating important differences in biology. To obtain a more accurate map of the human BM we then retrained the mouse ANN using scRNA-Seq data from a limited sample of human BM cells. Typically, less than 10 human cells of a given type were needed to accurately learn its representation in the updated model. In some cases, human cell identities could be inferred directly from the mouse ANN without retraining, via a process of biologically-guided zero-shot learning. These results show how machine learning can be used to reconstruct complex biology from limited data and have broad implications for biomedical research.

scholarly journals Thyroid dysfunction and semen quality

2018 ◽  
Vol 32 ◽  
pp. 205873841877524 ◽  
Author(s):  
Sandro La Vignera ◽  
Roberto Vita
Keyword(s):  
Thyroid Hormones ◽  
Sperm Morphology ◽  
Semen Quality ◽  
Cell Types ◽  
Future Research ◽  
Thyroid Function Tests ◽  
Murine Models ◽  
Sperm Density ◽  
Semen Volume ◽  
Different Cell Types

Thyroid hormones act on testis in multiple ways and exert their effect on different cell types, including Leydig and Sertoli cells, and germ cells. An excess or deficit of thyroid hormones results in alterations of testis function, including semen abnormalities. More frequently, hyperthyroidism has been associated with reduced semen volume and reduced sperm density, motility, and morphology, whereas hypothyroidism is associated with reduced sperm morphology. Therefore, thyroid function tests should be part of the diagnostic workup of the infertile man. This article is aimed at (1) elucidating how hyperthyroidism and hypothyroidism lead to a reduction in semen quality, briefly reviewing the current literature on murine models and humans, and (2) pinpointing the limitations of the studies carried out so far and identifying new perspectives for future research.

Study of the Molecular Architecture of Keratin Filaments by Electron Microscopy

1982 ◽  
Vol 40 ◽  
pp. 118-119
Author(s):  
U. Aebi ◽  
P. Rew ◽  
T.-T. Sun
Keyword(s):  
Electron Microscopy ◽  
Structural Organization ◽  
Cell Types ◽  
Structural Features ◽  
Molecular Architecture ◽  
The Past ◽  
Keratin Filaments ◽  
Different Types ◽  
10 Nm Filaments ◽  
Different Cell Types

Various types of intermediate-sized (10-nm) filaments have been found and described in many different cell types during the past few years. Despite the differences in the chemical composition among the different types of filaments, they all yield common structural features: they are usually up to several microns long and have a diameter of 7 to 10 nm; there is evidence that they are made of several 2 to 3.5 nm wide protofilaments which are helically wound around each other; the secondary structure of the polypeptides constituting the filaments is rich in ∞-helix. However a detailed description of their structural organization is lacking to date.

Processing and Characterization of Recombinant von Willebrand Factor Expressed in Different Cell Types Using a Vaccinia Virus Vector

1992 ◽  
Vol 67 (01) ◽  
pp. 154-160 ◽  
Author(s):  
P Meulien ◽  
M Nishino ◽  
C Mazurier ◽  
K Dott ◽  
G Piétu ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Von Willebrand Factor ◽  
Human Fibroblasts ◽  
Active Form ◽  
Cell Types ◽  
Biologically Active ◽  
L Cells ◽  
Von Willebrand ◽  
Different Cell Types ◽  
Willebrand Factor

SummaryThe cloning of the cDNA encoding von Willebrand factor (vWF) has revealed that it is synthesized as a large precursor (pre-pro-vWF) molecule and it is now clear that the prosequence or vWAgll is responsible for the intracellular multimerization of vWF. We have cloned the complete vWF cDNA and expressed it using a recombinant vaccinia virus as vector. We have characterized the structure and function of the recombinant vWF (rvWF) secreted from five different cell types: baby hamster kidney (BHK), Chinese hamster ovary (CHO), human fibroblasts (143B), mouse fibroblasts (L) and primary embryonic chicken cells. Forty-eight hours after infection, the quantity of vWF antigen found in the cell supernatant varied from 3 to 12 U/dl depending on the cell type. By SDS-agarose gel electrophoresis, the percentage of high molecular weight forms of vWF varied from 39 to 49% relative to normal plasma for BHK, CHO, 143B and chicken cells but was less than 10% for L cells. In all cell types, the two anodic subbands of each multimer were missing. The two cathodic subbands were easily detected only in BHK and L cells. By SDS-PAGE of reduced samples, pro-vWF was present in similar quantity to the fully processed vWF subunit in L cells, present in moderate amounts in BHK and CHO and in very low amounts in 143B and chicken cells. rvWF from all cells bound to collagen and to platelets in the presence of ristocetin, the latter showing a high correlation between binding efficiency and degree of multimerization. rvWF from all cells was also shown to bind to purified FVIII and in this case binding appeared to be independent of the degree of multimerization. We conclude that whereas vWF is naturally synthesized only by endothelial cells and megakaryocytes, it can be expressed in a biologically active form from various other cell types.

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