scholarly journals Systemic gene expression profiles according to pain types in individuals with chronic spinal cord injury

2021 ◽  
Vol 17 ◽  
pp. 174480692110072
Author(s):  
Debra Morrison ◽  
Anthony A Arcese ◽  
Janay Parrish ◽  
Katie Gibbs ◽  
Andrew Beaufort ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cord Injury ◽  
Upregulated Genes

Pain affects most individuals with traumatic spinal cord injury (SCI). Major pain types after SCI are neuropathic or nociceptive, often experienced concurrently. Pain after SCI may be refractory to treatments and negatively affects quality of life. Previously, we analyzed whole blood gene expression in individuals with chronic SCI compared to able-bodied (AB) individuals. Most participants with SCI reported pain (N = 19/28). Here, we examined gene expression of participants with SCI by pain status. Compared to AB, participants with SCI with pain had 468 differentially expressed (DE) genes; participants without pain had 564 DE genes (FDR < 0.05). Among DE genes distinct to participants with SCI with pain, Gene Ontology Biological Process (GOBP) analysis showed upregulated genes were enriched in categories related to T cell activation or inflammation; downregulated genes were enriched in categories related to protein proteolysis and catabolism. Although most participants with pain reported multiple pain types concurrently, we performed a preliminary comparison of gene expression by worst pain problem type. Compared to AB, participants with SCI who ranked neuropathic (N = 9) as worst had one distinct DE gene (TMEM156); participants who ranked nociceptive (N = 10) as worst had 61 distinct DE genes (FDR < 0.05). In the nociceptive group, the GOBP category with the lowest P-value identified among upregulated genes was “positive regulation of T cell activation”; among downregulated genes it was “receptor tyrosine kinase binding”. An exploratory comparison of pain groups by principal components analysis also showed that the nociceptive group was enriched in T-cell related genes. A correlation analysis identified genes significantly correlated with pain intensity in the neuropathic or nociceptive groups (N = 145, 65, respectively, Pearson’s correlation r > 0.8). While this pilot study highlights challenges of identifying gene expression profiles that correlate with specific types of pain in individuals with SCI, it suggests that T-cell signaling should be further investigated in this context.

scholarly journals Reclassification of classic T cell subsets and identification of novel cell types by single-cell RNA sequencing

2020 ◽  
Author(s):  
Xiangru Shen ◽  
Xuefei Wang ◽  
Shan Chen ◽  
Hongyi Liu ◽  
Ni Hong ◽  
...  
Keyword(s):  
T Cell ◽  
Single Cell ◽  
Rna Sequencing ◽  
T Cell Activation ◽  
Cell Activation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Types ◽  
T Cell Subsets ◽  
Single Cell Rna Sequencing

Abstract Single cell RNA sequencing (scRNA-seq) clusters cells using genome-wide gene expression profiles. The relationship between scRNA-seq Clustered-Populations (scCPops) and cell surface marker-defined classic T cell subsets is unclear. Here, we interrogated 6 bead-enriched T cell subsets with 62,235 single cell transcriptomes and re-grouped them into 9 scCPops. Bead-enriched CD4 Naïve, CD8 Naïve and CD4 memory were mainly clustered into their scCPop counterparts, while the other T cell subsets were clustered into multiple scCPops including unexpected mucosal-associated invariant T cell and natural killer T cell. Most interestingly, we discovered a new T cell type that highly expressed Interferon Signaling Associated Genes (ISAGs), namely IFNhi T. We further enriched IFNhi T for scRNA-seq analyses. IFNhi T cluster disappeared on tSNE after removing ISAGs, and IFNhi T cluster showed up by tSNE analyses of ISAGs alone, indicating ISAGs are the major contributor of IFNhi T cluster. BST2+ cells and BST2- cells showing different efficiencies of T cell activation indicates high ISAGs may contribute to quick immune responses.

scholarly journals Identification Of Exosomal LncRNAs From Peripheral Blood In Spinal Cord Injury Mouse Model

2021 ◽  
Author(s):  
Jian-an Li ◽  
Ming-peng Shi ◽  
Lin Cong ◽  
Ming-yu Gu ◽  
Yi-heng Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Peripheral Blood ◽  
Regulatory Networks ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Repair Process ◽  
Neurological Dysfunction ◽  
Cord Injury ◽  
Non Coding Rnas

Abstract Background Spinal Cord Injury ( SCI ) is a disease leading to permanent neurological dysfunction. In recent years, exosomes and non-coding RNAs have been considered as potential therapeutic agents for spinal cord injury. Based on ceRNA regulatory network, the role of non-coding RNAs has been paid attention to, and some genes related to the pathological process after spinal cord injury have been found. However, most gene studies only focus on exosomes and non-coding RNAs in spinal cord injury sites, and few genes related to spinal cord injury repair have been found. Objective We aimed to identify exosomes and non-coding RNA in peripheral blood after spinal cord injury, and to predict its role in spinal cord injury according to gene expression profiles. Materials and methods After successful modeling of spinal cord injury, rat exosomes were extracted from peripheral blood.Western-Blot was used to identify exosomes. After RNA was extracted from exosomes, total transcriptome sequencing and differential gene GO and KEGG Pathway analysis were performed. We selected potential genes for quantitative Real-Time PCR (qRT-PCR) assays and predicted their potential regulatory networks. Results The successful establishment of spinal cord injury model was confirmed by Tarlov’s scores, and the extracted exosomes were confirmed by Western-Blot and electron microscopy. Among the significantly differentially expressed lncRNAs, XR_351404, XR_353833, XR_590719, XR_590076, and XR_591455 were associated with miRNA related to repair after spinal cord injury. Conclusions The regulatory effect of this network may play a key role in the repair process of SCI. The differential lncRNAs we found may serve as therapeutic targets and diagnostic biomarkers for SCI.

scholarly journals Screening Circular RNA Related to Vascular Endothelial Proliferation, Migration and Angiogenesis in Spinal Cord Injury by RNA Sequencing

2020 ◽  
Author(s):  
Xin Ye ◽  
Yilei Chen ◽  
Jiasheng Wang ◽  
Jian Chen ◽  
Ying Yao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Early Stage ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Circular Rnas ◽  
Vascular Endothelial ◽  
Endothelial Proliferation ◽  
Cord Injury

Abstract Background: Traumatic spinal cord injury (SCI) causes high rates of worldwide morbidity because of the complex secondary injury. Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs, which have recently been recognized as important regulators of gene expression and pathological processes. In this study, we have attempted to elucidate the expression profiles of circRNAs in a mouse model of SCI and comprehensively understand vascular endothelial proliferation, migration and angiogenesis in the early stage of secondary injury.Methods: Deep RNA sequencing (RNA-seq) and bioinformatic analysis including GO enrichment analysis, KEGG pathway analysis and circRNA-miRNA-mRNA network construction were performed to investigate the expression patterns of circRNAs in mouse spinal cord after SCI (n= 3 per group) for three days and explore the differentially expressed circRNAs related to vascular endothelial proliferation, migration and angiogenesis. Results: Total of 1288 circRNAs were altered (>2-fold change, p<0.05) in the spinal cord after SCI, including 991 were upregulated and 297 were downregulated. Meanwhile we constructed a circRNA-mRNA network to predict their functions for circRNAs can act as “miRNA sponges”,. We next analyzed the altered circRNAs related to vascular endothelial proliferation, migration and angiogenesis by GO and KEGG analyses. 121 circRNAs were found to correlating to vascular endothelial proliferation，migration and angiogenesis in spinal cord after SCI. Conclusions: Our results reveal that circRNAs locally regulate their related protein-gene expression and play key roles in the vascular endothelial proliferation, migration and angiogenesis of SCI.

scholarly journals Gene Expression Profiles Analyzed Using Integrating RNA Sequencing, and Microarray Reveals Increased Inflammatory Response, Proliferation, and Osteoclastogenesis in Pigmented Villonodular Synovitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yang Zhao ◽  
Jiaoyun Lv ◽  
Hongwei Zhang ◽  
Jiawei Xie ◽  
Hui Dai ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell Activation ◽  
Cell Activation ◽  
Expression Profiles ◽  
Osteoclast Differentiation ◽  
Gene Expression Profiles ◽  
Myeloid Cell ◽  
Pigmented Villonodular Synovitis ◽  
Villonodular Synovitis ◽  
Pigmented Villonodular

BackgroundPigmented villonodular synovitis (PVNS) is a rare condition that involves benign proliferation of the synovial tissue and is characterized by severe joint destruction and high recurrence even after surgical resection. However, poor understanding of the pathogenesis limits its effective therapy.MethodIn this study, gene expression profiles of six patients with PVNS, 11 patients with osteoarthritis (OA), nine patients with rheumatoid arthritis (RA) (E-MTAB-6141), and three healthy subjects (GSE143514) were analyzed using integrating RNA sequencing (RNA-seq) and microarray to investigate the PVNS transcriptome. Gene ontology, string, and cytoscape were used to determine the gene functional enrichment. Cell functional molecules were detected using flow cytometry or immunohistochemical test to identify the cell subset and function. CD14+ cells were isolated and induced to osteoclast to evaluate the monocyte/macrophage function.ResultsThe most obvious local manifestations of PVNS were inflammation, including increased immune cells infiltration and cytokine secretion, and tumor phenotypes. High proportion of inflammatory cells, including T cells, natural killer (NK) cells, NKT cells, and B cells were recruited from the blood. Th17 and monocytes, especially classical monocytes but not nonclassical monocytes, increased in PVNS synovium. An obvious increase in osteoclastogenesis and macrophage activation was observed locally. Elevated expression of MMP9, SIGLEC 15, and RANK were observed in myeloid cell of PVNS than OA. When compared with RA, osteoclast differentiation and myeloid cell activation are PVNS-specific characters, whereas T cell activation is shared by PVNS and RA.ConclusionThe transcriptional expression characteristics of PVNS showed increased immune response, cell migration, and osteoclastogenesis. Osteoclast differentiation is only observed in PVNS but not RA, whereas T-cell activation is common in inflammatory arthritis.

scholarly journals Integrative analysis of transcriptomic data for identification of T-cell activation-related mRNA signatures indicative of preterm birth

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jae Young Yoo ◽  
Do Young Hyeon ◽  
Yourae Shin ◽  
Soo Min Kim ◽  
Young-Ah You ◽  
...  
Keyword(s):  
Preterm Birth ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Sequencing Analysis ◽  
Mortality And Morbidity ◽  
Activation Pathway ◽  
The Core

AbstractPreterm birth (PTB), defined as birth at less than 37 weeks of gestation, is a major determinant of neonatal mortality and morbidity. Early diagnosis of PTB risk followed by protective interventions are essential to reduce adverse neonatal outcomes. However, due to the redundant nature of the clinical conditions with other diseases, PTB-associated clinical parameters are poor predictors of PTB. To identify molecular signatures predictive of PTB with high accuracy, we performed mRNA sequencing analysis of PTB patients and full-term birth (FTB) controls in Korean population and identified differentially expressed genes (DEGs) as well as cellular pathways represented by the DEGs between PTB and FTB. By integrating the gene expression profiles of different ethnic groups from previous studies, we identified the core T-cell activation pathway associated with PTB, which was shared among all previous datasets, and selected three representative DEGs (CYLD, TFRC, and RIPK2) from the core pathway as mRNA signatures predictive of PTB. We confirmed the dysregulation of the candidate predictors and the core T-cell activation pathway in an independent cohort. Our results suggest that CYLD, TFRC, and RIPK2 are potentially reliable predictors for PTB.

scholarly journals Whole blood vs PBMC: compartmental differences in gene expression profiling exemplified in asthma

2019 ◽  
Vol 15 (1) ◽  
Author(s):  
Daniel He ◽  
Chen Xi Yang ◽  
Basak Sahin ◽  
Amrit Singh ◽  
Casey P. Shannon ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
T Cell Activation ◽  
Whole Blood ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Research Subjects ◽  
Peripheral Blood Mononuclear

Abstract Background Blood has proven to be a useful resource for molecular analysis in numerous biomedical studies, with peripheral blood mononuclear cells (PBMCs) and whole blood being the major specimen types. However, comparative analyses between these two major compartments (PBMCs and whole blood) are few and far between. In this study, we compared gene expression profiles of PBMCs and whole blood samples obtained from research subjects with or without mild allergic asthma. Methods Whole blood (PAXgene) and PBMC samples were obtained from 5 mild allergic asthmatics and 5 healthy controls. RNA from both sample types was measured for expression of 730 immune-related genes using the NanoString nCounter platform. Results We identified 64 uniquely expressed transcripts in whole blood that reflected a variety of innate, humoral, and adaptive immune processes, and 13 uniquely expressed transcripts in PBMCs which were representative of T-cell and monocyte-mediated processes. Furthermore, analysis of mild allergic asthmatics versus non-asthmatics revealed 47 differentially expressed transcripts in whole blood compared to 1 differentially expressed transcript in PBMCs (FDR < 0.25). Finally, through simultaneous measurement of PBMC proteins on the nCounter assay, we identified CD28 and OX40 (TNFRSF4), both of which are critical co-stimulatory molecules during T-cell activation, as significantly upregulated in asthmatics. Conclusions Whole blood RNA preserved in PAXgene tubes is excellent for producing gene expression data with minimal variability and good sensitivity, suggesting its utility in multi-centre studies requiring measurement of blood gene expression.

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