Migraine-associated gene expression in cell types of the central and peripheral nervous system

Cephalalgia ◽  
2019 ◽  
Vol 40 (5) ◽  
pp. 517-523
Author(s):  
Angeliki Vgontzas ◽  
William Renthal
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Single Cell ◽  
Rna Sequencing ◽  
Peripheral Nervous System ◽  
Cell Types ◽  
Genome Wide Association Studies ◽  
Single Cell Rna Sequencing ◽  
The Central Nervous System ◽  
System Cell

Background Genome-wide association studies have implicated dozens of genes with migraine susceptibility, but it remains unclear in which nervous system cell types these genes are expressed. Methods Using single-cell RNA sequencing data from the central and peripheral nervous system, including the trigeminal ganglion, the expression of putative migraine-associated genes was compared across neuronal, glial and neurovascular cell types within these tissues. Results Fifty-four putative migraine-associated genes were expressed in the central nervous system, peripheral nervous system or neurovascular cell types analyzed. Six genes (11.1%) were selectively enriched in central nervous system cell types, three (5.5%) in neurovascular cell types, and two (3.7%) in peripheral nervous system cell types. The remaining genes were expressed in multiple cell types. Conclusions Single-cell RNA sequencing of the brain and peripheral nervous system localizes each migraine-associated gene to its respective nervous system tissue and the cell types in which it is expressed. While the majority of migraine-associated genes are broadly expressed, we identified several cell-type-specific migraine-associated genes in the central nervous system, peripheral nervous system, and neurovasculature. Trial registration: not applicable.

scholarly journals Microglia response following acute demyelination is heterogeneous and limits infiltrating macrophage dispersion

2020 ◽  
Vol 6 (3) ◽  
pp. eaay6324 ◽  
Author(s):  
Jason R. Plemel ◽  
Jo Anne Stratton ◽  
Nathan J. Michaels ◽  
Khalil S. Rawji ◽  
Eric Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Sciatic Nerve ◽  
Single Cell ◽  
Peripheral Inflammation ◽  
Macrophage Response ◽  
Single Cell Rna Sequencing ◽  
Privileged Status ◽  
The Central Nervous System

Microglia and infiltrating macrophages are thought to orchestrate the central nervous system (CNS) response to injury; however, the similarities between these cells make it challenging to distinguish their relative contributions. We genetically labeled microglia and CNS-associated macrophages to distinguish them from infiltrating macrophages. Using single-cell RNA sequencing, we describe multiple microglia activation states, one of which was enriched for interferon associated signaling. Although blood-derived macrophages acutely infiltrated the demyelinated lesion, microglia progressively monopolized the lesion environment where they surrounded infiltrating macrophages. In the microglia-devoid sciatic nerve, the infiltrating macrophage response was sustained. In the CNS, the preferential proliferation of microglia and sparse microglia death contributed to microglia dominating the lesion. Microglia ablation reversed the spatial restriction of macrophages with the demyelinated spinal cord, highlighting an unrealized macrophages-microglia interaction. The restriction of peripheral inflammation by microglia may be a previously unidentified mechanism by which the CNS maintains its “immune privileged” status.

scholarly journals Defensive Perimeter in the Central Nervous System: Predominance of Astrocytes and Astrogliosis during Recovery from Varicella-Zoster Virus Encephalitis

2015 ◽  
Vol 90 (1) ◽  
pp. 379-391 ◽  
Author(s):  
John E. Carpenter ◽  
Amy C. Clayton ◽  
Kevin C. Halling ◽  
Daniel J. Bonthius ◽  
Erin M. Buckingham ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Human Brain ◽  
Varicella Zoster Virus ◽  
Peripheral Nervous System ◽  
Cellular Response ◽  
Cell Types ◽  
Varicella Zoster ◽  
Human Host ◽  
The Central Nervous System

ABSTRACTVaricella-zoster virus (VZV) is a highly neurotropic virus that can cause infections in both the peripheral nervous system and the central nervous system. Several studies of VZV reactivation in the peripheral nervous system (herpes zoster) have been published, while exceedingly few investigations have been carried out in a human brain. Notably, there is no animal model for VZV infection of the central nervous system. In this report, we characterized the cellular environment in the temporal lobe of a human subject who recovered from focal VZV encephalitis. The approach included not only VZV DNA/RNA analyses but also a delineation of infected cell types (neurons, microglia, oligodendrocytes, and astrocytes). The average VZV genome copy number per cell was 5. Several VZV regulatory and structural gene transcripts and products were detected. When colocalization studies were performed to determine which cell types harbored the viral proteins, the majority of infected cells were astrocytes, including aggregates of astrocytes. Evidence of syncytium formation within the aggregates included the continuity of cytoplasm positive for the VZV glycoprotein H (gH) fusion-complex protein within a cellular profile with as many as 80 distinct nuclei. As with other causes of brain injury, these results suggested that astrocytes likely formed a defensive perimeter around foci of VZV infection (astrogliosis). Because of the rarity of brain samples from living humans with VZV encephalitis, we compared our VZV results with those found in a rat encephalitis model following infection with the closely related pseudorabies virus and observed similar perimeters of gliosis.IMPORTANCEInvestigations of VZV-infected human brain from living immunocompetent human subjects are exceedingly rare. Therefore, much of our knowledge of VZV neuropathogenesis is gained from studies of VZV-infected brains obtained at autopsy from immunocompromised patients. These are not optimal samples with which to investigate a response by a human host to VZV infection. In this report, we examined both flash-frozen and paraffin-embedded formalin-fixed brain tissue of an otherwise healthy young male with focal VZV encephalitis, most likely acquired from VZV reactivation in the trigeminal ganglion. Of note, the cellular response to VZV infection mimicked the response to other causes of trauma to the brain, namely, an ingress of astrocytes and astrogliosis around an infectious focus. Many of the astrocytes themselves were infected; astrocytes aggregated in clusters. We postulate that astrogliosis represents a successful defense mechanism by an immunocompetent human host to eliminate VZV reactivation within neurons.

scholarly journals Building an RNA Sequencing Transcriptome of the Central Nervous System

2016 ◽  
Vol 22 (6) ◽  
pp. 579-592 ◽  
Author(s):  
Xiaomin Dong ◽  
Yanan You ◽  
Jia Qian Wu
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
Rna Sequencing ◽  
Large Scale ◽  
Expression Profiles ◽  
Cell Types ◽  
Specific Cell ◽  
Rna Seq ◽  
The Central Nervous System

The composition and function of the central nervous system (CNS) is extremely complex. In addition to hundreds of subtypes of neurons, other cell types, including glia (astrocytes, oligodendrocytes, and microglia) and vascular cells (endothelial cells and pericytes) also play important roles in CNS function. Such heterogeneity makes the study of gene transcription in CNS challenging. Transcriptomic studies, namely the analyses of the expression levels and structures of all genes, are essential for interpreting the functional elements and understanding the molecular constituents of the CNS. Microarray has been a predominant method for large-scale gene expression profiling in the past. However, RNA-sequencing (RNA-Seq) technology developed in recent years has many advantages over microarrays, and has enabled building more quantitative, accurate, and comprehensive transcriptomes of the CNS and other systems. The discovery of novel genes, diverse alternative splicing events, and noncoding RNAs has remarkably expanded the complexity of gene expression profiles and will help us to understand intricate neural circuits. Here, we discuss the procedures and advantages of RNA-Seq technology in mammalian CNS transcriptome construction, and review the approaches of sample collection as well as recent progress in building RNA-Seq-based transcriptomes from tissue samples and specific cell types.

scholarly journals Excel Template for Identifying Mouse Myeloid Cell-Types in the Central Nervous System Based on Single-Cell RNA Sequencing Data

2021 ◽  
Author(s):  
He-zuo Lü ◽  
Xin-Yi Lyu ◽  
Jing-Lu Li ◽  
Shu-Qin Ding ◽  
Jian-Guo Hu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Single Cell ◽  
Rna Sequencing ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Gene Markers ◽  
Cell Clusters ◽  
Significant Difference ◽  
Single Cell Rna Sequencing

Abstract Background The myeloid cells play a vital role in health and disease of central nervous system (CNS). However, how to clearly distinguish them is still a knotty problem. At present, single-cell RNA Sequencing (scRNA-Seq) technology can sequence thousands of cells at the single-cell level, and then divide the cells into different clusters according to the similarity of gene expression, but it is still difficult to further identity these cell clusters. Generally, there are some specific marker genes for cell-type identities. However, it is difficult to distinguish a variety of myeloid cells in the CNS, because these cells often have the same or cross gene markers, and some markers will change significantly in different pathological states. Therefore, establishing a simple and practical method to distinguish these cell populations is of great significance for the analysis of scRNA-Seq data. Methods Referring to CellMarker (http://biocc.hrbmu.edu.cn/CellMarker/), PanglaoDB (https://panglaodb.se/) and Mouse Cell Atlas (http://bis.zju.edu.cn/MCA/gallery.html), combining with the recent literatures, a simple Excel template was designed, in which a panel of gene makers corresponding to the myeloid cells were included. The 83 cell clusters from several recently reported single-cell data were used to verify the accuracy of this template. Results This template could easily distinguish myeloid cell-subtypes and non-myeloid cells. Comparing with literatures, the overall consistency rate was 93.98%. There was no statistically significant difference between the two groups (Bowker’s test, P >0.05). Kappa symmetric measures showed that the Kappa value = 0.642 (P < 0.01). Conclusions The cell identities of scRNA-Seq cluster data could be performed using our simple Excel formulae, a panel of gene markers and ideal cell clustering data are the basis for accurate identification of CNS myeloid cell-subtypes.

scholarly journals Single-Cell RNA Sequencing Reveals the Diversity of the Immunological Landscape following Central Nervous System Infection by a Murine Coronavirus

2020 ◽  
Vol 94 (24) ◽  
Author(s):  
Amber R. Syage ◽  
H. Atakan Ekiz ◽  
Dominic D. Skinner ◽  
Colleen Stone ◽  
Ryan M. O’Connell ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Responses ◽  
Viral Infection ◽  
Single Cell ◽  
Rna Sequencing ◽  
Host Defense ◽  
Molecular Signatures ◽  
Single Cell Rna Sequencing ◽  
Murine Coronavirus

ABSTRACT Intracranial (i.c.) infection of susceptible C57BL/6 mice with the neurotropic JHM strain of mouse hepatitis virus (JHMV) (a member of the Coronaviridae family) results in acute encephalomyelitis and viral persistence associated with an immune-mediated demyelinating disease. The present study was undertaken to better understand the molecular pathways evoked during innate and adaptive immune responses as well as the chronic demyelinating stage of disease in response to JHMV infection of the central nervous system (CNS). Using single-cell RNA sequencing analysis (scRNAseq) on flow-sorted CD45-positive (CD45+) cells enriched from brains and spinal cords of experimental mice, we demonstrate the heterogeneity of the immune response as determined by the presence of unique molecular signatures and pathways involved in effective antiviral host defense. Furthermore, we identify potential genes involved in contributing to demyelination as well as remyelination being expressed by both microglia and macrophages. Collectively, these findings emphasize the diversity of the immune responses and molecular networks at defined stages following viral infection of the CNS. IMPORTANCE Understanding the immunological mechanisms contributing to both host defense and disease following viral infection of the CNS is of critical importance given the increasing number of viruses that are capable of infecting and replicating within the nervous system. With this in mind, the present study was undertaken to evaluate the molecular signatures of immune cells within the CNS at defined times following infection with a neuroadapted murine coronavirus using scRNAseq. This approach has revealed that the immunological landscape is diverse, with numerous immune cell subsets expressing distinct mRNA expression profiles that are, in part, dictated by the stage of infection. In addition, these findings reveal new insight into cellular pathways contributing to control of viral replication as well as to neurologic disease.

scholarly journals Lysosomal Storage Diseases-Regulating Neurodegeneration

2015 ◽  
Vol 9s2 ◽  
pp. JEN.S25475 ◽  
Author(s):  
Rob U. Onyenwoke ◽  
Jay E. Brenman
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Pompe Disease ◽  
Lysosomal Storage Diseases ◽  
Cell Types ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
The Central Nervous System ◽  
Made In

Autophagy is a complex pathway regulated by numerous signaling events that recycles macromolecules and can be perturbed in lysosomal storage diseases (LSDs). The concept of LSDs, which are characterized by aberrant, excessive storage of cellular material in lysosomes, developed following the discovery of an enzyme deficiency as the cause of Pompe disease in 1963. Great strides have since been made in better understanding the biology of LSDs. Defective lysosomal storage typically occurs in many cell types, but the nervous system, including the central nervous system and peripheral nervous system, is particularly vulnerable to LSDs, being affected in two-thirds of LSDs. This review provides a summary of some of the better characterized LSDs and the pathways affected in these disorders.

Glucuronyl 3-sulfate occurs exclusively on distal unmyelinated terminals of selected sensory neurons in the peripheral nervous system

1995 ◽  
Vol 53 ◽  
pp. 958-959
Author(s):  
S.S. Spicer ◽  
B.A. Schulte
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Sensory Nerves ◽  
Tissue Antigens ◽  
The Central Nervous System ◽  
The Brain ◽  
Leu 7

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.

scholarly journals Single-cell data clustering based on sparse optimization and low-rank matrix factorization

2021 ◽  
Author(s):  
Yinlei Hu ◽  
Bin Li ◽  
Falai Chen ◽  
Kun Qu
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Matrix Factorization ◽  
Data Clustering ◽  
Cell Types ◽  
Low Rank ◽  
Sequencing Data ◽  
Rank Matrix ◽  
Single Cell Rna Sequencing ◽  
Low Rank Matrix

Abstract Unsupervised clustering is a fundamental step of single-cell RNA sequencing data analysis. This issue has inspired several clustering methods to classify cells in single-cell RNA sequencing data. However, accurate prediction of the cell clusters remains a substantial challenge. In this study, we propose a new algorithm for single-cell RNA sequencing data clustering based on Sparse Optimization and low-rank matrix factorization (scSO). We applied our scSO algorithm to analyze multiple benchmark datasets and showed that the cluster number predicted by scSO was close to the number of reference cell types and that most cells were correctly classified. Our scSO algorithm is available at https://github.com/QuKunLab/scSO. Overall, this study demonstrates a potent cell clustering approach that can help researchers distinguish cell types in single-cell RNA sequencing data.

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