scholarly journals Deconvolution of heterogeneous wound tissue samples into relative macrophage phenotype compositionviamodels based on gene expression

2017 ◽  
Vol 9 (4) ◽  
pp. 328-338 ◽  
Author(s):  
Nicole M. Ferraro ◽  
Will Dampier ◽  
Michael S. Weingarten ◽  
Kara L. Spiller
Keyword(s):  
Gene Expression ◽  
Macrophage Phenotype ◽  
Tissue Samples ◽  
Wound Tissue

scholarly journals Genes associated with inflammation and bone remodeling are highly expressed in the bone of patients with the early-stage cam-type femoroacetabular impingement

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Guanying Gao ◽  
Ruiqi Wu ◽  
Rongge Liu ◽  
Jianquan Wang ◽  
Yingfang Ao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Tissue ◽  
Bone Remodeling ◽  
Femoroacetabular Impingement ◽  
Early Stage ◽  
Control Group ◽  
Tissue Samples ◽  
Expression Levels ◽  
Normal Bone ◽  
Impingement Zone

Abstract Background Recent studies have shown high expression levels of certain inflammatory, anabolic, and catabolic genes in the articular cartilage from the impingement zone of the hips with femoroacetabular impingement (FAI), representing an increased metabolic state. Nevertheless, little is known about the molecular properties of bone tissue from the impingement zone of hips with FAI. Methods Bone tissue samples from patients with early-stage cam-type FAI were collected during hip arthroscopy for treatment of cam-type FAI. Control bone tissue samples were collected from six patients who underwent total hip replacement because of a femoral neck fracture. Quantitative real-time polymerase chain reaction (PCR) was performed to determine the gene expression associated with inflammation and bone remodeling. The differences in the gene expression in bone tissues from the patients with early-stage cam-type FAI were also evaluated based on clinical parameters. Results In all, 12 patients with early-stage cam-type FAI and six patients in the control group were included in this study. Compared to the control samples, the bone tissue samples from patients with FAI showed higher expression levels of interleukin-6 (IL-6), alkaline phosphatase (ALP), receptor activator of nuclear factor-kB ligand (RANKL), and osteoprotegerin (OPG) (P < 0.05). IL-1 expression was detected only in the control group. On the other hand, there was no significant difference in IL-8 expression between the patients with FAI and the control group. The patients with FAI having a body mass index (BMI) of >24 kg/m2 showed higher ALP expression (P < 0.05). Further, the expression of IL-6 and ALP was higher in the patients with FAI in whom the lateral center-edge angle was >30° (P < 0.05). Conclusions Our results indicated the metabolic condition of bone tissues in patients with early-stage cam-type FAI differed from that of normal bone in the femoral head-neck junction. The expression levels of the genes associated with inflammation and bone remodeling were higher in the bone tissue of patients with early-stage cam-type FAI than in the patients with normal bone tissue.

Abstract 190: Epigenetic Modifications of Pro-inflammatory Gene Expression in Macrophages by a Demethylase Enzyme, JMJD3, May Promote Chronic Inflammation in Type 2 Diabetic (T2D) Wounds

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Katherine A Gallagher ◽  
Amrita Joshi ◽  
William Carson ◽  
Dawn Coleman ◽  
Peter Henke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Chronic Inflammation ◽  
Histone Methylation ◽  
Gene Promoter ◽  
Epigenetic Modifications ◽  
Macrophage Phenotype ◽  
M1 Macrophage ◽  
Type 2 Diabetic

Introduction Type 2 diabetic(T2D) wounds are characterized by chronic inflammation, maintained by an exaggerated M1(pro-inflammatory) macrophage phenotype response. We seek to define a link between epigenetic modifications of bone marrow(BM) cells in T2D and dysregulated macrophages in wounds. We hypothesized that a chromatin modifying demethylase enzyme, JMJD3, is responsible for the decrease in H3K27me3 repressive methylation at the IL-12 gene promoter and thus drives an M1 macrophage phenotype in T2D wounds. Methods BM/adipose tissue(AT)/wounds were harvested from 30 diet-induced obese mice(DIO)(MG= 350g/DL) and 30 matched(WT) controls. For chromatin immunoprecipitation(ChIP) analysis, cells were isolated via ferromagnetic columns(CD34+,CD11b+). ChIP to detect histone methylation at the promoter regions of JMJD3 and IL-12(key M1 macrophage gene) was performed and RNA analysis was done with standard primers. Results JMJD3 mRNA in the BM is significantly increased in the DIO versus WT. ChIP showed increased H3K4me3(gene expression mark) in CD34+ progenitor cells and a corresponding decrease in H3K27me3(repressive mark) in monocytes at the promoter region of JMJD3. These changes correspond with the decrease in H3K27me3 seen at the IL-12 promoter in macrophages(CD11b+) from AT/T2D wounds. Conclusions Epigenetic changes initiated by JMJD3 in BM progenitor cells result in changes in histone methylation at the IL-12 promoter favoring an M1 phenotype in macrophages and thus contributes to the chronic inflammation seen in T2D wounds and AT. Whether manipulation of epigenetic enzymes could reduce chronic inflammation in T2D wounds requires further work.

scholarly journals Expression of EGF receptors in canine prostate with proliferative inflammatory atrophy and carcinoma

2017 ◽  
Vol 47 (12) ◽  
Author(s):  
Mariana Batista Rodrigues Faleiro ◽  
Lorena Cardoso Cintra ◽  
Rosália Santos Amorim Jesuino ◽  
Eugênio Gonçalves de Araújo ◽  
Rafael Malagoli Rocha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Product ◽  
Normal Tissue ◽  
Prostatic Carcinoma ◽  
Prostatic Tissue ◽  
Egf Receptors ◽  
Tissue Samples ◽  
Proliferative Inflammatory Atrophy ◽  
Erbb2 Mrna

ABSTRACT: Gene expression of ErbB1 and ErbB2, and immunostaining of EGFR (Her1) and Her2 (c-erbB-2) were evaluated in this study to ascertain whether these receptors are involved in the evolution of canine premalignant and malignant prostatic lesions, as proliferative inflammatory atrophy (PIA) and prostatic carcinoma (PC). With regards to the intensity of EGFR immunostaining, there was no difference between normal prostatic tissue and tissues with PIA or PC. In relation to Her2 immunostaining, there were differences between normal prostatic tissue and those with PIA and PC, as also differences between prostates with PIA and PC. There was no correlation between EGFR and Her2 immunostaining. ErbB1 gene product was detected in two normal tissue samples, in one with PIA, and in all samples with PC. ErbB2 mRNA was recorded in two canine samples with PIA, in all with PC, but was not detected in normal prostatic tissue. It was concluded that EGFR and Her2 play roles in canine PIA and PC, suggesting that those receptors may be involved in canine prostatic carcinogenesis.

scholarly journals Identification of miRNAs and genes for predicting Barrett’s esophagus progressing to esophageal adenocarcinoma using miRNA-mRNA integrated analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260353
Author(s):  
Chengjiao Yao ◽  
Yilin Li ◽  
Lihong Luo ◽  
Qin Xiong ◽  
Xiaowu Zhong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Barrett’S Esophagus ◽  
Esophageal Adenocarcinoma ◽  
Barrett's Esophagus ◽  
Trp Channels ◽  
Functional Enrichment ◽  
Integrated Analysis ◽  
Epstein Barr Virus Infection ◽  
Tissue Samples ◽  
Microarray Datasets

Barrett’s esophagus (BE) is defined as any metaplastic columnar epithelium in the distal esophagus, which predisposes to esophageal adenocarcinoma (EAC). Yet, the mechanism through which BE develops to EAC still remain unclear. Moreover, the miRNA-mRNA regulatory network in distinguishing BE from EAC still remains poorly understood. To identify differentially expressed miRNAs (DEMs) and genes (DEGs) between EAC and BE from tissue samples, gene expression microarray datasets GSE13898, GSE26886, GSE1420 and miRNA microarray datasets GSE16456, GSE20099 were downloaded from Gene Expression Omnibus (GEO) database. GEO2R was used to screen the DEMs and DEGs. Pathway and functional enrichment analysis were performed by DAVID database. The protein–protein interaction (PPI) network was constructed by STRING and been visualized by Cytoscape software. Finnal, survival analysis was performed basing TCGA database. A total of 21 DEMs were identified. The enriched functions and pathways analysis inclued Epstein-Barr virus infection, herpesvirus infection and TRP channels. GART, TNFSF11, GTSE1, NEK2, ICAM1, PSMD12, CTNNB1, CDH1, PSEN1, IL1B, CTNND1, JAG1, CDH17, ITCH, CALM1 and ITGA6 were considered as the hub-genes. Hsa-miR-143 and hsa-miR-133b were the highest connectivity target gene. JAG1 was predicted as the largest number of target miRNAs. The expression of hsa-miR-181d, hsa-miR-185, hsa-miR-15b, hsa-miR-214 and hsa-miR-496 was significantly different between normal tissue and EAC. CDH1, GART, GTSE1, NEK2 and hsa-miR-496, hsa-miR-214, hsa-miR-15b were found to be correlated with survival.

scholarly journals Tissue-specific evaluation of suitable reference genes for RT-qPCR in the pond snail, Lymnaea stagnalis

2019 ◽  
Author(s):  
Alexander P Young ◽  
Carmen F Landry ◽  
Daniel J Jackson ◽  
Russell C Wyeth
Keyword(s):  
Gene Expression ◽  
Reference Genes ◽  
Lymnaea Stagnalis ◽  
Elongation Factor ◽  
Pond Snail ◽  
Tissue Samples ◽  
Systematic Assessment ◽  
Wide Range ◽  
The Stability ◽  
Suitable Reference

Reverse transcription quantitative PCR (RT-qPCR) is a robust technique for the quantification and comparison of gene expression across multiple tissues. To obtain reliable results, one or more reference genes must be employed to normalize expression measurements among treatments or tissue samples. Candidate reference genes must be validated to ensure that they are stable prior to use in qPCR experiments. The pond snail (Lymnaea stagnalis) is a common research organism, particularly in the areas of learning and memory, and is an emerging target for qPCR experimentation. However, no systematic assessment of reference genes has been performed in this animal. Therefore, the aim of our research was to identify stable reference genes to normalize gene expression data from a variety of tissues in L. stagnalis. We evaluated a panel of seven reference genes across six different tissues in L. stagnalis with RT-qPCR. The genes included: elongation factor 1-alpha (EF1α), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), beta-actin (ACTB), beta-tubulin (TUBB), ubiquitin (UBI), prenylated rab acceptor protein 1 (Rapac1), and a voltage gated potassium channel (VGKC). These genes exhibited a wide range of expression levels among tissues. The stability of each of the genes was consistent when measured by any of the standard stability assessment algorithms: geNorm, NormFinder, BestKeeper and RefFinder. Our data indicate that GAPDH and EF1α are highly stable in the tissues that we examined (central nervous system, tentacles, lips, penis, foot, mantle) as well as in pooled analyses. We do not recommend VGKC for use in RT-qPCR experiments due to its relatively low expression stability. Our results were generally congruent with those obtained from similar studies in other molluscs. Given that a minimum of two reference genes are recommended for data normalization, we suggest GAPDH and EF1α are a strong option for multi-tissue analyses of RT-qPCR data in Lymnaea stagnalis.

scholarly journals Systematic analysis of the literature in search of defining systemic sclerosis subsets

2021 ◽  
pp. jrheum.201594
Author(s):  
Tatiana Nevskaya ◽  
Janet E. Pope ◽  
Matthew A. Turk ◽  
Jenny Shu ◽  
April Marquardt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Sclerosis ◽  
Original Data ◽  
Response To Therapy ◽  
Classification Systems ◽  
Skin Involvement ◽  
Multisystem Disease ◽  
Systematic Analysis ◽  
Tissue Samples ◽  
Gene Expression Signatures

Objective Systemic sclerosis (SSc) is a multisystem disease with heterogeneity in presentation and prognosis. An international collaboration to develop new SSc subset criteria is underway. Our objectives were to identify systems of SSc subset classification and synthesize novel concepts to inform development of new criteria. Methods Medline, Cochrane MEDLINE, CINAHL, EMBASE and Web of Science were searched from their inceptions to December 2019 for studies related to SSc sub-classification, limited to humans without language or sample size restrictions. Results Of 5686 citations, 102 articles reported original data on SSc subsets. Subset classification systems relied on extent of skin involvement and/or scleroderma-specific autoantibodies (n=61), nailfold capillary patterns (n=29), molecular, genomic and cellular patterns (n=12). While some systems of subset classification confer prognostic value for clinical phenotype, severity, and mortality; only subsetting by gene expression signatures in tissue samples has been associated with response to therapy. Conclusion Subsetting on extent of skin involvement remains important. Novel disease attributes including SSc-specific autoantibodies, nailfold capillary patterns and tissue gene expression signatures have been proposed as innovative means of SSc subsetting.

scholarly journals Bayesian Framework for Detecting Gene Expression Outliers in Individual Samples

2020 ◽  
pp. 160-170
Author(s):  
John Vivian ◽  
Jordan M. Eizenga ◽  
Holly C. Beale ◽  
Olena M. Vaske ◽  
Benedict Paten
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Rna Seq ◽  
Single Patient ◽  
Tissue Samples ◽  
Composite Tissue ◽  
Patient Sample ◽  
Statistical Framework ◽  
Therapeutic Leads ◽  
Upregulated Genes

PURPOSE Many antineoplastics are designed to target upregulated genes, but quantifying upregulation in a single patient sample requires an appropriate set of samples for comparison. In cancer, the most natural comparison set is unaffected samples from the matching tissue, but there are often too few available unaffected samples to overcome high intersample variance. Moreover, some cancer samples have misidentified tissues of origin or even composite-tissue phenotypes. Even if an appropriate comparison set can be identified, most differential expression tools are not designed to accommodate comparisons to a single patient sample. METHODS We propose a Bayesian statistical framework for gene expression outlier detection in single samples. Our method uses all available data to produce a consensus background distribution for each gene of interest without requiring the researcher to manually select a comparison set. The consensus distribution can then be used to quantify over- and underexpression. RESULTS We demonstrate this method on both simulated and real gene expression data. We show that it can robustly quantify overexpression, even when the set of comparison samples lacks ideally matched tissue samples. Furthermore, our results show that the method can identify appropriate comparison sets from samples of mixed lineage and rediscover numerous known gene-cancer expression patterns. CONCLUSION This exploratory method is suitable for identifying expression outliers from comparative RNA sequencing (RNA-seq) analysis for individual samples, and Treehouse, a pediatric precision medicine group that leverages RNA-seq to identify potential therapeutic leads for patients, plans to explore this method for processing its pediatric cohort.

scholarly journals A Study of Gene Expression Changes in Human Spinal and Oculomotor Neurons; Identifying Potential Links to Sporadic ALS

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 448
Author(s):  
Aayan N. Patel ◽  
Dennis Mathew
Keyword(s):  
Gene Expression ◽  
Disease Progression ◽  
Motor Neurons ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Tissue Samples ◽  
Disease Symptoms ◽  
Sporadic Als ◽  
Oculomotor Neurons ◽  
Als Patients

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that causes compromised function of motor neurons and neuronal death. However, oculomotor neurons are largely spared from disease symptoms. The underlying causes for sporadic ALS as well as for the resistance of oculomotor neurons to disease symptoms remain poorly understood. In this bioinformatic-analysis, we compared the gene expression profiles of spinal and oculomotor tissue samples from control individuals and sporadic ALS patients. We show that the genes GAD2 and GABRE (involved in GABA signaling), and CALB1 (involved in intracellular Ca2+ ion buffering) are downregulated in the spinal tissues of ALS patients, but their endogenous levels are higher in oculomotor tissues relative to the spinal tissues. Our results suggest that the downregulation of these genes and processes in spinal tissues are related to sporadic ALS disease progression and their upregulation in oculomotor neurons confer upon them resistance to ALS symptoms. These results build upon prevailing models of excitotoxicity that are relevant to sporadic ALS disease progression and point out unique opportunities for better understanding the progression of neurodegenerative properties associated with sporadic ALS.

scholarly journals 1450-1545 Young Investigator Awards & Presentations Basic/Translational Exploring cellular subpopulations in glioblastoma and matched organoids using single-cell RNA-seq 52

2018 ◽  
Vol 45 (S3) ◽  
pp. S13-S14
Author(s):  
VG LeBlanc ◽  
D Trinh ◽  
M Hughes ◽  
I Luthra ◽  
D Livingstone ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Tissue Sample ◽  
Expression Patterns ◽  
Model Systems ◽  
Sequencing Data ◽  
Tissue Samples ◽  
Original Tumour ◽  
Current Therapies ◽  
Intratumoural Heterogeneity

Glioblastomas (GBMs) account for nearly half of all primary malignant brain tumours, and current therapies are often only marginally effective. Our understanding of the underlying biology of these tumours and the development of new therapies have been complicated in part by widespread inter- and intratumoural heterogeneity. To characterize this heterogeneity, we performed regional subsampling of primary glioblastomas and derived organoids from these tissue samples. We then performed single-cell RNA-sequencing (scRNA-seq) on these primary regional subsamples and 1-3 matched organoids per sample. We have profiled samples from six tumour sets to date and have obtained sequencing data for 21,234 primary tissue cells and 14,742 organoid cells. While the most apparent differences in gene expression appear to be between individual tumours, we were also able to identify similar cellular subpopulations across tissue samples and across organoids. Importantly, organoids derived from the same tissue sample appeared to be composed of similar cellular subpopulations and were highly comparable to each other, indicating that replicate organoids faithfully represent the original tumour tissue. Overall, our scRNA-seq approach will help evaluate the utility of tumour-derived organoids as model systems for GBM and will aid in identifying cellular subpopulations defined by gene expression patterns, both in primary GBM regional subsamples and their associated organoids. These analyses will allow for the characterization of clonal or subclonal populations that are likely to respond to different therapeutic approaches and may also uncover novel therapeutic targets previously unrevealed through bulk analyses.

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