scholarly journals Single-Cell Transcriptome Profiling Unravels Distinct Peripheral Blood Immune Cell Signatures of RRMS and MOG Antibody-Associated Disease

2022 ◽  
Vol 12 ◽  
Author(s):  
Ju Liu ◽  
Xiaoyan Yang ◽  
Jiali Pan ◽  
Zhihua Wei ◽  
Peidong Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Single Cell ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Serum Antibody ◽  
Clinical Manifestations ◽  
Demyelinating Diseases ◽  
Inflammatory Monocytes ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Relapsing-remitting multiple sclerosis (RRMS) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) are inflammatory demyelinating diseases of the central nervous system (CNS). Due to the shared clinical manifestations, detection of disease-specific serum antibody of the two diseases is currently considered as the gold standard for the diagnosis; however, the serum antibody levels are unpredictable during different stages of the two diseases. Herein, peripheral blood single-cell transcriptome was used to unveil distinct immune cell signatures of the two diseases, with the aim to provide predictive discrimination. Single-cell RNA sequencing (scRNA-seq) was conducted on the peripheral blood from three subjects, i.e., one patient with RRMS, one patient with MOGAD, and one patient with healthy control. The results showed that the CD19+ CXCR4+ naive B cell subsets were significantly expanded in both RRMS and MOGAD, which was verified by flow cytometry. More importantly, RRMS single-cell transcriptomic was characterized by increased naive CD8+ T cells and cytotoxic memory-like Natural Killer (NK) cells, together with decreased inflammatory monocytes, whereas MOGAD exhibited increased inflammatory monocytes and cytotoxic CD8 effector T cells, coupled with decreased plasma cells and memory B cells. Collectively, our findings indicate that the two diseases exhibit distinct immune cell signatures, which allows for highly predictive discrimination of the two diseases and paves a novel avenue for diagnosis and therapy of neuroinflammatory diseases.

scholarly journals Single-cell transcriptome analysis of the immunosuppressive effect of differential expression of tumor PD-L1 on responding TCR-T cells

2020 ◽  
Author(s):  
Renpeng Ding ◽  
Shang Liu ◽  
Shanshan Wang ◽  
Huanyi Chen ◽  
Fei Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Tumor Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Gene Clusters ◽  
Cellular Assays ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

AbstractPD-L1 expression levels in tumors do not consistently predict cancer patients’ response to PD-(L)1 inhibitors. We therefore evaluated how tumor PD-L1 levels affect the anti-PD-(L)1 efficacy and T cell function. We used MART-1-specific TCR-T cells (TCR-TMART-1) stimulated with MART-127-35 peptide-loaded MEL-526 tumor cells with different proportions of them expressing PD-L1 to perform cellular assays and high-throughput single-cell RNA sequencing. Compared to control T cells, TCR-TMART-1 were more sensitive to exhaustion and secreted lower pro-inflammatory but higher anti-inflammatory cytokines with increasing proportions of PD-L1+ tumor cells. The colocalization of T cells and tumor cells in gene clusters correlated negatively with the proportion of PD-L1+ tumor cells and positively with immune cell cytotoxicity. Moreover, elevated proportion of PD-L1+ tumor cells increased PD-L1 expression and decreased PD-1 expression on T cells and enhanced T cell death. The expression of PD-1 and PD-L1 in T cells and macrophages also correlated positively with COVID-19 severity.

scholarly journals Landscape Of M6a RNA Methylation Regulators and Tumor Microenvironment Cell-Infiltration Characterization In Gastroesophageal Adenocarcinomas

2021 ◽  
Author(s):  
Duanrui Liu ◽  
Jingyu Zhu ◽  
Zongming Wang ◽  
Yusong Fang ◽  
Mingjie Yuan ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Rna Methylation ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Abstract Background: RNA N6-methyladenosine (m6A) modification plays a nonnegligible role in shaping individual tumor microenvironment (TME) characterizations. However, the landscape and relationship of m6A modification and TME cell infiltration remain unknown in gastroesophageal adenocarcinomas (GEA). Methods: We systematically examined the TME of GEA focusing on the distinct m6A modification patterns from the public databases. Intrinsic patterns of m6A modification were evaluated for associations with clinicopathological characteristics, underlying biological pathways, tumor immune cell infiltration, oncological outcomes and treatment responses. We generated a single-cell transcriptome atlas of the GEA sample inhouse to validate the role of the m6A modification pattern on TME.Results: We identified and validated the landscape of m6A regulators and tumor-infiltrating immune cells in GEA. Then, two distinct m6A modification patterns of GEA (cluster1/2 subgroup) were defined, and we correlated two subgroups with TME cell-infiltrating characteristics. Cluster2 subgroup correlates with a poorer prognosis, down-regulated PD-1 expression, higher risk scores and distinct immune cell infiltration. Additionally, PPI and WGCNA network analysis were integrated to identify key module genes closely related to immune infiltration of GEA to find immunotherapy markers. And COL4A1 and COL5A2 in brown module were significantly correlated to the prognosis, PD-1/L1 and CTLA-4 expression of GEA patients. Interesting, low COL5A2 expression was linked to an enhanced response to anti-PD-1 immunotherapy. Finally, a prognostic risk score was constructed using three m6A regulator-associated signatures that represented an independent prognosis factor for GEA. The single-cell transcriptome atlas of GEA sample validated the role of m6A modification pattern on TME and revealed that three m6A regulators are highly expressed in CD4+ T cells, CD8+ T cells, Tregs and Macrophages.Conclusions: Our work revealed m6A RNA methylation regulators are a type of vital participant in the malignant progression and TME diversity of GEA. m6A modification patterns of COL5A2 may be the potential biomarker contributes to predicting the response to anti-PD-1 immunotherapy.

scholarly journals A Single-Cell Transcriptome Profiling of Anterior Kidney Leukocytes From Nile Tilapia (Oreochromis niloticus)

2021 ◽  
Vol 12 ◽  
Author(s):  
Liting Wu ◽  
Along Gao ◽  
Lan Li ◽  
Jianlin Chen ◽  
Jun Li ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Single Cell ◽  
Nile Tilapia ◽  
Immune Cell ◽  
Cell Types ◽  
Cell Transcriptome ◽  
B Cell Subsets ◽  
Single Cell Transcriptome

Teleost fish anterior kidney (AK) is an important hematopoietic organ with multifarious immune cells, which have immune functions comparable to mammalian bone marrow. Myeloid and lymphoid cells locate in the AK, but the lack of useful specific gene markers and antibody-based reagents for the cell subsets makes the identification of the different cell types difficult. Single-cell transcriptome sequencing enables single-cell capture and individual library construction, making the study on the immune cell heterogeneity of teleost fish AK possible. In this study, we examined the transcriptional patterns of 11,388 AK leukocytes using 10× Genomics single-cell RNA sequencing (scRNA-seq). A total of 22 clusters corresponding to five distinct immune cell subsets were identified, which included B cells, T cells, granulocytes, macrophages, and dendritic cells (DCs). However, the subsets of myeloid cells (granulocytes, macrophages, and DCs) were not identified in more detail according to the known specific markers, even though significant differences existed among the clusters. Thereafter, we highlighted the B-cell subsets and identified them as pro/pre B cells, immature/mature B cells, activated B/plasmablasts, or plasma cells based on the different expressions of the transcription factors (TFs) and cytokines. Clustering of the differentially modulated genes by pseudo-temporal trajectory analysis of the B-cell subsets showed the distinct kinetics of the responses of TFs to cell conversion. Moreover, we classified the T cells and discovered that CD3+CD4−CD8−, CD3+CD4+CD8+, CD4+CD8−, and CD4−CD8+ T cells existed in AK, but neither CD4+CD8− nor CD4−CD8+ T cells can be further classified into subsets based on the known TFs and cytokines. Pseudotemporal analysis demonstrated that CD4+CD8− and CD4−CD8+ T cells belonged to different states with various TFs that might control their differentiation. The data obtained above provide a valuable and detailed resource for uncovering the leukocyte subsets in Nile tilapia AK, as well as more potential markers for identifying the myeloid and lymphoid cell types.

scholarly journals Single-Cell Mass Cytometry on Peripheral Blood Identifies Immune Cell Subsets Associated with Primary Biliary Cholangitis

2020 ◽  
Author(s):  
Jin Sung Jang ◽  
Brian Juran ◽  
Kevin Y. Cunningham ◽  
Vinod K. Gupta ◽  
YoungMin Son ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Single Cell ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Memory B Cells ◽  
Primary Biliary Cholangitis ◽  
Mass Cytometry ◽  
Peripheral Immune System

AbstractThe relationship between Primary Biliary Cholangitis (PBC), a chronic cholestatic autoimmune liver disease, and the peripheral immune system remains to be fully understood. Herein, we performed the first mass cytometry (CyTOF)-based, immunophenotyping analysis of the peripheral immune system in PBC at single-cell resolution. CyTOF was performed on peripheral blood mononuclear cells (PBMCs) from PBC patients (n=33) and age-/sex-matched healthy controls (n=33) to obtain immune cell abundance and marker expression profiles. Hiearchical clustering methods were applied to identify immune cell types and subsets significantly associated with PBC. Subsets of gamma-delta T cells (CD3+TCRgd+), CD8+ T cells (CD3+CD8+CD161+PD1+), and memory B cells (CD3-CD19+CD20+CD24+CD27+) were found to have lower abundance in PBC than in control. In contrast, higher abundance of subsets of monocytes and naïve B cells were observed in PBC compared to control. Furthermore, several naïve B cell (CD3-CD19+CD20+CD24-CD27-) subsets were significantly higher in PBC patients with cirrhosis (indicative of late-stage disease) than in those without cirrhosis. Alternatively, subsets of CD8+CD161+ T cells and memory B cells were lower in abundance in cirrhotic relative to non-cirrhotic PBC patients. Future immunophenotyping investigations could lead to better understanding of PBC pathogenesis and progression, and also to the discovery of novel biomarkers and treatment strategies.

scholarly journals Single-Cell RNA Sequencing of Peripheral Blood Reveals Immune Cell Signatures in Alzheimer’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Hui Xu ◽  
Jianping Jia
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Single Cell ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Adaptive Immune Response ◽  
Immune Repertoire ◽  
Adaptive Immune ◽  
Peripheral Immune Cells

The peripheral immune system is thought to affect the pathology of the central nervous system in Alzheimer’s disease (AD). However, current knowledge is inadequate for understanding the characteristics of peripheral immune cells in AD. This study aimed to explore the molecular basis of peripheral immune cells and the features of adaptive immune repertoire at a single cell level. We profiled 36,849 peripheral blood mononuclear cells from AD patients with amyloid-positive status and normal controls with amyloid-negative status by 5’ single-cell transcriptome and immune repertoire sequencing using the cell ranger standard analysis procedure. We revealed five immune cell subsets: CD4+ T cells, CD8+ T cells, B cells, natural killer cells, and monocytes–macrophages cells, and disentangled the characteristic alterations of cell subset proportion and gene expression patterns in AD. Thirty-one cell type-specific key genes, comprising abundant human leukocyte antigen genes, and multiple immune-related pathways were identified by protein–protein interaction network and pathway enrichment analysis. We also found high-frequency amplification clonotypes in T and B cells and decreased diversity in T cells in AD. As clone amplification suggested the activation of an adaptive immune response against specific antigens, we speculated that the peripheral adaptive immune response, especially mediated by T cells, may have a role in the pathogenesis of AD. This finding may also contribute to further research regarding disease mechanism and the development of immune-related biomarkers or therapy.

scholarly journals Single-cell atlas of a non-human primate reveals new pathogenic mechanisms of COVID-19

2020 ◽  
Author(s):  
Lei Han ◽  
Xiaoyu Wei ◽  
Chuanyu Liu ◽  
Giacomo Volpe ◽  
Zhifeng Wang ◽  
...  
Keyword(s):  
Single Cell ◽  
Viral Entry ◽  
Immune Cell ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
List Type ◽  
Innate Immune Responses ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome ◽  
Substantial Heterogeneity

ABSTRACTStopping COVID-19 is a priority worldwide. Understanding which cell types are targeted by SARS-CoV-2 virus, whether interspecies differences exist, and how variations in cell state influence viral entry is fundamental for accelerating therapeutic and preventative approaches. In this endeavor, we profiled the transcriptome of nine tissues from a Macaca fascicularis monkey at single-cell resolution. The distribution of SARS-CoV-2 facilitators, ACE2 and TMRPSS2, in different cell subtypes showed substantial heterogeneity across lung, kidney, and liver. Through co-expression analysis, we identified immunomodulatory proteins such as IDO2 and ANPEP as potential SARS-CoV-2 targets responsible for immune cell exhaustion. Furthermore, single-cell chromatin accessibility analysis of the kidney unveiled a plausible link between IL6-mediated innate immune responses aiming to protect tissue and enhanced ACE2 expression that could promote viral entry. Our work constitutes a unique resource for understanding the physiology and pathophysiology of two phylogenetically close species, which might guide in the development of therapeutic approaches in humans.Bullet pointsWe generated a single-cell transcriptome atlas of 9 monkey tissues to study COVID-19.ACE2+TMPRSS2+ epithelial cells of lung, kidney and liver are targets for SARS-CoV-2.ACE2 correlation analysis shows IDO2 and ANPEP as potential therapeutic opportunities.We unveil a link between IL6, STAT transcription factors and boosted SARS-CoV-2 entry.

Linking the T cell receptor to the single cell transcriptome in antigen‐specific human T cells

2016 ◽  
Vol 94 (6) ◽  
pp. 604-611 ◽  
Author(s):  
Auda A Eltahla ◽  
Simone Rizzetto ◽  
Mehdi R Pirozyan ◽  
Brigid D Betz‐Stablein ◽  
Vanessa Venturi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Human T Cells ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation

Science ◽  
2019 ◽  
Vol 363 (6425) ◽  
pp. eaat7554 ◽  
Author(s):  
Marta Joana Costa Jordão ◽  
Roman Sankowski ◽  
Stefanie M. Brendecke ◽  
Sagar ◽  
Giuseppe Locatelli ◽  
...  
Keyword(s):  
Single Cell ◽  
Immune Cell ◽  
Myeloid Cell ◽  
Innate Immune ◽  
Functional Studies ◽  
Cell Diversity ◽  
Single Cell Profiling ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

The innate immune cell compartment is highly diverse in the healthy central nervous system (CNS), including parenchymal and non-parenchymal macrophages. However, this complexity is increased in inflammatory settings by the recruitment of circulating myeloid cells. It is unclear which disease-specific myeloid subsets exist and what their transcriptional profiles and dynamics during CNS pathology are. Combining deep single-cell transcriptome analysis, fate mapping, in vivo imaging, clonal analysis, and transgenic mouse lines, we comprehensively characterized unappreciated myeloid subsets in several CNS compartments during neuroinflammation. During inflammation, CNS macrophage subsets undergo self-renewal, and random proliferation shifts toward clonal expansion. Last, functional studies demonstrated that endogenous CNS tissue macrophages are redundant for antigen presentation. Our results highlight myeloid cell diversity and provide insights into the brain’s innate immune system.

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