scholarly journals Differential coexpression in human tissues and the confounding effect of mean expression levels

2018 ◽  
Author(s):  
Marjan Farahbod ◽  
Paul Pavlidis
Keyword(s):  
Human Tissues ◽  
Confounding Effect ◽  
Expression Levels ◽  
Differential Coexpression

scholarly journals Localization of Cytochrome P450 CYP2S1 Expression in Human Tissues by In Situ Hybridization and Immunohistochemistry

2005 ◽  
Vol 53 (5) ◽  
pp. 549-556 ◽  
Author(s):  
Sirkku T. Saarikoski ◽  
Harriet A.-L. Wikman ◽  
Gillian Smith ◽  
C. Henrik J. Wolff ◽  
Kirsti Husgafvel-Pursiainen
Keyword(s):  
Cytochrome P450 ◽  
In Situ Hybridization ◽  
Epithelial Cells ◽  
Cellular Localization ◽  
Tumor Development ◽  
Tissue Microarrays ◽  
Cell Types ◽  
Human Tissues ◽  
Expression Levels

CYP2S1 is a recently discovered dioxin-inducible member of the cytochrome P450 superfamily. It has been shown to be involved in the metabolism of some aromatic hydrocarbons as well as retinoic acid, suggesting a role in biotransformation of both exogenous and endogenous compounds. In this study, we used mRNA in situ hybridization and immunohistochemistry to investigate the cellular localization of CYP2S1 in various human tissues using tissue microarrays. High expression levels were observed mainly in epithelial cell types, especially in the epithelia frequently exposed to xenobiotics. In the respiratory tract, the expression was strong in nasal cavity, bronchi, and bronchioli, whereas it was low in the alveolar lining cells. Similarly, CYP2S1 was highly expressed in the epithelial cells throughout the gastrointestinal tract. Strong epithelial expression was also observed in uterine cervix, urinary bladder, and skin. In many exocrine glands (e.g., adrenal gland and pancreas), secretory epithelial cells showed moderate to strong expression levels. In the liver, the expression was low. CYP2S1 was highly expressed in epithelial cells that are major targets for carcinogen exposure and common progenitor cells to tumor development. Indeed, we found strong CYP2S1 expression in many tumors of epithelial origin.

GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues

2005 ◽  
Vol 21 (3) ◽  
pp. 389-395 ◽  
Author(s):  
Robert D. Barber ◽  
Dan W. Harmer ◽  
Robert A. Coleman ◽  
Brian J. Clark
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Gene Expression Data ◽  
Internal Control ◽  
Housekeeping Genes ◽  
Housekeeping Gene ◽  
Human Tissues ◽  
Expression Data ◽  
Expression Levels ◽  
Gapdh Mrna

Quantitative gene expression data are often normalized to the expression levels of control or so-called “housekeeping” genes. An inherent assumption in the use of housekeeping genes is that expression of the genes remains constant in the cells or tissues under investigation. Although exceptions to this assumption are well documented, housekeeping genes are of value in fully characterized systems. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is one of the most commonly used housekeeping genes used in comparisons of gene expression data. To investigate the value of GAPDH as a housekeeping gene in human tissues, the expression of GAPDH mRNA was measured in a panel of 72 different pathologically normal human tissue types. Measurements were obtained from 371,088 multiplexed, quantitative real-time RT-PCRs with specific target genes. Significant differences in the expression levels of GAPDH mRNA were observed between tissue types and between donors of the same tissue. A 15-fold difference in GAPDH mRNA copy numbers was observed between the highest and lowest expressing tissue types, skeletal muscle and breast, respectively. No specific effect of either age or gender was observed on GAPDH mRNA expression. These data provide an extensive analysis of GAPDH mRNA expression in human tissues and confirm previous reports of the marked variability of GAPDH expression between tissue types. These data establish comparative levels of expression and can be used to add value to gene expression data in which GAPDH is used as the internal control.

scholarly journals Comparative Analysis of Cytokine mRNA Expressions in Human Tissues with Mycobacterium tuberculosis Infection

2021 ◽  
Author(s):  
Sung-Bae Park ◽  
Heechul Park ◽  
Yoon-Sung Choi ◽  
Ji Young Park ◽  
Dongsup Lee ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mrna Expression ◽  
The Body ◽  
Molecular Diagnostic ◽  
Human Tissues ◽  
Immune Markers ◽  
Cytokine Mrna ◽  
Expression Levels ◽  
Gm Csf ◽  
Mrna Expression Levels

In the present study, we aimed to investigate whether an automated molecular diagnostic method based on PCR-reverse blot hybridization assay can discriminate between human Mycobacterium tuberculosis (MTB)-positive and -negative FFPE tissues and to compare the relative mRNA expression levels of various host immune markers between MTB-infected and uninfected human tissues using quantitative reverse transcription (qRT) PCR. A total of 52 human FFPE tissue samples from various regions of the body, including the lungs, lymph nodes, tendons, colon, and appendix, were collected and used for the molecular identification of Mycobacterium species and analysis of cytokine mRNA expression. As a result, IFN-γ, TNF-α, IP-10, CXCL9, CXCL11, and GM-CSF mRNA expression levels in MTB-infected tissues were significantly higher than those in uninfected samples. Additionally, the differences in the mRNA expression levels of IFN-γ, CXCL9, and GM-CSF between MTB-infected and uninfected tissues were statistically significant were statistically significant (p < 0.05). Correlation curve analysis indicated that the mRNA expression of IFN-γ was inversely proportional to that of IP-10 and that the mRNA expression levels of IFN-γ, TNF-α, CXCL9, CXCL11, GM-CSF, and TNFR were proportional and well-correlated. Furthermore, to establish marker profiles for detecting MTB infection, the statistically significant expression levels of three markers were combined. We confirmed that the combined profile of IFN-γ, CXCL9, and GM-CSF expression levels was statistically significant (P < 0.001). Although the mRNA expression patterns of host immune markers may vary according to MTB infection status, these patterns may be highly correlated and can be simultaneously used as an additional indicator for diagnosing TB.

scholarly journals Ectopic HOTTIP Expression Induces Non-canonical Transactivation Pathways to Promote Growth and Invasiveness in Pancreatic Ductal Adenocarcinoma

2019 ◽  
Author(s):  
Chi Hin Wong ◽  
Chi Han Li ◽  
Qifang He ◽  
Stephen Lam Chan ◽  
Joanna Hung-Man Tong ◽  
...  
Keyword(s):  
Cell Growth ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Invasion ◽  
Regulatory Mechanism ◽  
Ductal Adenocarcinoma ◽  
Human Tissues ◽  
Expression Levels ◽  
Genome Wide Analysis ◽  
Oncogenic Pathway ◽  
Genome Wide

AbstractLncRNA HOTTIP (HOXA transcript at the distal tip) is upregulated in pancreatic ductal adenocarcinoma (PDAC). However, oncogenic pathway mediated by HOTTIP is not fully understood. We identified canonical HOTTIP-HOXA13 targets: CYP26B1, CLIC5, CHI3L1 and UCP2 which were responsible for cell growth and cell invasion. Importantly, genome-wide analysis revealed that 38% of the genes regulated by HOTTIP contained H3K4me3 and HOTTIP enrichment at their promoters, without HOXA13 binding. HOTTIP complexed with WDR5-MLL1 to trans-activate oncogenic proteins CYB5R2, SULT1A1, KIF26A, SLC1A4 and TSC22D1 through directly triggering H3K4me3 at their promoters. The WDR5, MLL1 and H3K4me3 levels at their promoters and their expression levels were sensitive to HOTTIP overexpression and knockdown. These suggested the importance of non-canonical trans-acting HOTTIP-WDR5-MLL1 pathway in HOTTIP-regulatory mechanism by promoting the expression of oncogenic proteins. Furthermore, we dissected the mechanism by which HOTTIP was regulated by miR-497 in PDAC. Analysis of PDAC human tissues also revealed that HOTTIP was negatively correlated with miR-497 level. Our findings demonstrated that HOTTIP, upregulated in PDAC due to the loss of inhibitory miR-497, promoted PDAC progression through canonical HOTTIP-HOXA13 axis and a novel non-canonical trans-acting HOTTIP-WDR5-MLL1-H3K4me3 pathway.

scholarly journals Identifying pathways and networks associated with the SARS-CoV-2 cell receptor ACE2 based on gene expression profiles in human tissues

2020 ◽  
Author(s):  
Qiushi Feng ◽  
Lin Li ◽  
Xiaosheng Wang
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Receptor ◽  
Immune Defense ◽  
Human Tissues ◽  
Expression Levels ◽  
Expression Correlation ◽  
Host Cell Receptor ◽  
Positive Expression

Abstract The angiotensin-converting enzyme 2 (ACE2) is a host cell receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has infected more than six million people worldwide and has caused more than 370,000 deaths as of May 31, 2020. An investigation of ACE2 expression in human tissues may provide insights into the mechanism of SARS-CoV-2 infection. We identified pathways associated with ACE2 expression and gene co-expression networks of ACE2 in pan-tissue based on the gene expression profiles in human tissues. We found that the pathways significantly associated with ACE2 upregulation were mainly involved in immune, stromal signature, metabolism, cell growth and proliferation, and cancer and other diseases. The number of genes having a significant positive expression correlation with ACE2 in females far exceeded that in males. The estrogen receptors (ESR1 and ESR2) and androgen receptor (AR) genes had a significant positive expression correlation with ACE2 in pan-tissue. Meanwhile, the enrichment levels of immune cells were positively associated with the expression levels of ESR1 and ESR2, while they were inversely associated with the expression levels of AR in pan-tissue and in multiple individual tissues. It suggests that females are likely to have a more robust immune defense system against SARS-CoV-2 than males, partially explaining why females have better clinical outcomes of SARS-CoV-2 infections than males. Our data warrant further investigation for understanding the mechanism of SARS-CoV-2 infection.

scholarly journals An RNA structure-mediated, posttranscriptional model of human α-1-antitrypsin expression

2017 ◽  
Vol 114 (47) ◽  
pp. E10244-E10253 ◽  
Author(s):  
Meredith Corley ◽  
Amanda Solem ◽  
Gabriela Phillips ◽  
Lela Lackey ◽  
Benjamin Ziehr ◽  
...  
Keyword(s):  
Protein Expression ◽  
Rna Structure ◽  
Genetic Alterations ◽  
Luciferase Reporter ◽  
Human Tissues ◽  
Mrna Isoforms ◽  
Expression Levels ◽  
Regulatory Program ◽  
Antitrypsin Deficiency ◽  
Reporter Assays

Chronic obstructive pulmonary disease (COPD) affects over 65 million individuals worldwide, where α-1-antitrypsin deficiency is a major genetic cause of the disease. The α-1-antitrypsin gene, SERPINA1, expresses an exceptional number of mRNA isoforms generated entirely by alternative splicing in the 5′-untranslated region (5′-UTR). Although all SERPINA1 mRNAs encode exactly the same protein, expression levels of the individual mRNAs vary substantially in different human tissues. We hypothesize that these transcripts behave unequally due to a posttranscriptional regulatory program governed by their distinct 5′-UTRs and that this regulation ultimately determines α-1-antitrypsin expression. Using whole-transcript selective 2′-hydroxyl acylation by primer extension (SHAPE) chemical probing, we show that splicing yields distinct local 5′-UTR secondary structures in SERPINA1 transcripts. Splicing in the 5′-UTR also changes the inclusion of long upstream ORFs (uORFs). We demonstrate that disrupting the uORFs results in markedly increased translation efficiencies in luciferase reporter assays. These uORF-dependent changes suggest that α-1-antitrypsin protein expression levels are controlled at the posttranscriptional level. A leaky-scanning model of translation based on Kozak translation initiation sequences alone does not adequately explain our quantitative expression data. However, when we incorporate the experimentally derived RNA structure data, the model accurately predicts translation efficiencies in reporter assays and improves α-1-antitrypsin expression prediction in primary human tissues. Our results reveal that RNA structure governs a complex posttranscriptional regulatory program of α-1-antitrypsin expression. Crucially, these findings describe a mechanism by which genetic alterations in noncoding gene regions may result in α-1-antitrypsin deficiency.

scholarly journals Genetic effects on gene expression across human tissues

Nature ◽  
2017 ◽  
Vol 550 (7675) ◽  
pp. 204-213 ◽  
Author(s):  
Keyword(s):  
Gene Expression ◽  
Genetic Basis ◽  
Tissue Expression ◽  
Genetic Effects ◽  
Human Tissues ◽  
Cellular Mechanisms ◽  
Genetic Traits ◽  
Expression Levels ◽  
Gene Expression Levels

Abstract Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.

Microstructural comparison of synthetic bioceramics with natural bioceramics

1991 ◽  
Vol 49 ◽  
pp. 38-39
Author(s):  
Shulin Wen ◽  
Jingwei Feng ◽  
A. Krajewski ◽  
A. Ravaglioli
Keyword(s):  
Recent Work ◽  
Human Body ◽  
Human Tissues ◽  
Main Constituent ◽  
Laboratory Furnace ◽  
Chinese Adult ◽  
Human Enamel ◽  
Biological Compatibility ◽  
Synthetic Hydroxyapatite ◽  
Synthetic Work

Hydroxyapatite bioceramics has attracted many material scientists as it is the main constituent of the bone and the teeth in human body. The synthesis of the bioceramics has been performed for years. Nowadays, the synthetic work is not only focused on the hydroapatite but also on the fluorapatite and chlorapatite bioceramics since later materials have also biological compatibility with human tissues; and they may also be very promising for clinic purpose. However, in comparison of the synthetic bioceramics with natural one on microstructure, a great differences were observed according to our previous results. We have investigated these differences further in this work since they are very important to appraise the synthetic bioceramics for their clinic application.The synthetic hydroxyapatite and chlorapatite were prepared according to A. Krajewski and A. Ravaglioli and their recent work. The briquettes from different hydroxyapatite or chlorapatite powders were fired in a laboratory furnace at the temperature of 900-1300°C. The samples of human enamel selected for the comparison with synthetic bioceramics were from Chinese adult teeth.

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