scholarly journals FIN-Seq: Transcriptional profiling of specific cell types in frozen archived tissue from the human central nervous system

2019 ◽  
Author(s):  
Ryoji Amamoto ◽  
Emanuela Zuccaro ◽  
Nathan C. Curry ◽  
Sonia Khurana ◽  
Hsu-Hsin Chen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Single Cell ◽  
Human Tissue ◽  
Cell Types ◽  
Transcriptional Analysis ◽  
Specific Cell ◽  
Cell Type Specificity ◽  
Human Central Nervous System ◽  
Single Nucleus

ABSTRACTThousands of frozen, archived tissues from postmortem human central nervous system (CNS) are currently available in brain banks. As single cell and single nucleus technologies are beginning to elucidate the cellular diversity present within the human CNS, it is becoming clear that transcriptional analysis of the human CNS requires cell type specificity. Single cell and single nucleus RNA profiling provide one avenue to decipher this heterogeneity. An alternative, complementary approach is to profile isolated, pre-defined cell types and use methods that can be applied to many archived human tissue samples. Here, we developed FIN-Seq (FrozenImmunolabeledNucleiSequencing), a method that accomplishes these goals. FIN-Seq uses immunohisto-chemical isolation of nuclei of specific cell types from frozen human tissue, followed by RNA-Sequencing. We applied this method to frozen postmortem samples of human cerebral cortex and retina and were able to identify transcripts, including low abundance transcripts, in specific cell types.

scholarly journals FIN-Seq: transcriptional profiling of specific cell types from frozen archived tissue of the human central nervous system

2019 ◽  
Author(s):  
Ryoji Amamoto ◽  
Emanuela Zuccaro ◽  
Nathan C Curry ◽  
Sonia Khurana ◽  
Hsu-Hsin Chen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Rna Sequencing ◽  
Human Tissue ◽  
Transcriptional Profiling ◽  
Cell Types ◽  
Specific Cell ◽  
Human Central Nervous System ◽  
Tissue Samples ◽  
Rna Profiling

Abstract Thousands of frozen, archived tissue samples from the human central nervous system (CNS) are currently available in brain banks. As recent developments in RNA sequencing technologies are beginning to elucidate the cellular diversity present within the human CNS, it is becoming clear that an understanding of this diversity would greatly benefit from deeper transcriptional analyses. Single cell and single nucleus RNA profiling provide one avenue to decipher this heterogeneity. An alternative, complementary approach is to profile isolated, pre-defined cell types and use methods that can be applied to many archived human tissue samples that have been stored long-term. Here, we developed FIN-Seq (Frozen Immunolabeled Nuclei Sequencing), a method that accomplishes these goals. FIN-Seq uses immunohistochemical isolation of nuclei of specific cell types from frozen human tissue, followed by bulk RNA-Sequencing. We applied this method to frozen postmortem samples of human cerebral cortex and retina and were able to identify transcripts, including low abundance transcripts, in specific cell types.

The role of globins in cardiovascular physiology

2021 ◽  
Author(s):  
T.C. Steven Keller ◽  
Christophe Lechauve ◽  
Alexander S Keller ◽  
Steven Brooks ◽  
Mitchell J Weiss ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Central Nervous System ◽  
Nervous System ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Specific Cell ◽  
In Cells

Globin proteins exist in every cell type of the vasculature, from erythrocytes to endothelial cells, vascular smooth muscle cells, and peripheral nerve cells. Many globin subtypes are also expressed in muscle tissues (including cardiac and skeletal muscle), in other organ-specific cell types, and in cells of the central nervous system. The ability of each of these globins to interact with molecular oxygen (O2) and nitric oxide (NO) is preserved across these contexts. Endothelial α-globin is an example of extra-erythrocytic globin expression. Other globins, including myoglobin, cytoglobin, and neuroglobin are observed in other vascular tissues. Myoglobin is observed primarily in skeletal muscle and smooth muscle cells surrounding the aorta or other large arteries. Cytoglobin is found in vascular smooth muscle but can also be expressed in non-vascular cell types, especially in oxidative stress conditions after ischemic insult. Neuroglobin was first observed in neuronal cells, and its expression appears to be restricted mainly to the central and peripheral nervous systems. Brain and central nervous system neurons expressing neuroglobin are positioned close to many arteries within the brain parenchyma and can control smooth muscle contraction and, thus, tissue perfusion and vascular reactivity. Overall, reactions between NO and globin heme-iron contribute to vascular homeostasis by regulating vasodilatory NO signals and scaveging reactive species in cells of the mammalian vascular system. Here, we discuss how globin proteins affect vascular physiology with a focus on NO biology, and offer perspectives for future study of these functions.

scholarly journals Localization of phosphotyrosine adaptor protein ShcD/SHC4 in the adult rat central nervous system

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Hannah N. Robeson ◽  
Hayley R. Lau ◽  
Laura A. New ◽  
Jasmin Lalonde ◽  
John N. Armstrong ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Olfactory Bulb ◽  
Adaptor Protein ◽  
Cell Types ◽  
Olfactory Nerve ◽  
Adult Brain ◽  
Specific Cell ◽  
Adult Rat ◽  
Fiber Tracts

Abstract Background Mammalian Shc (Src homology and collagen) proteins comprise a family of four phosphotyrosine adaptor molecules which exhibit varied spatiotemporal expression and signaling functions. ShcD is the most recently discovered homologue and it is highly expressed in the developing central nervous system (CNS) and adult brain. Presently however, its localization within specific cell types of mature neural structures has yet to be characterized. Results In the current study, we examine the expression profile of ShcD in the adult rat CNS using immunohistochemistry, and compare with those of the neuronally enriched ShcB and ShcC proteins. ShcD shows relatively widespread distribution in the adult brain and spinal cord, with prominent levels of staining throughout the olfactory bulb, as well as in sub-structures of the cerebellum and hippocampus, including the subgranular zone. Co-localization studies confirm the expression of ShcD in mature neurons and progenitor cells. ShcD immunoreactivity is primarily localized to axons and somata, consistent with the function of ShcD as a cytoplasmic adaptor. Regional differences in expression are observed among neural Shc proteins, with ShcC predominating in the hippocampus, cerebellum, and some fiber tracts. Interestingly, ShcD is uniquely expressed in the olfactory nerve layer and in glomeruli of the main olfactory bulb. Conclusions Together our findings suggest that ShcD may provide a distinct signaling contribution within the olfactory system, and that overlapping expression of ShcD with other Shc proteins may allow compensatory functions in the brain.

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 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 616. Tailored Expression of a Transgene to Specific Cell Types in the Central Nervous System After Peripheral Injection of AAV9

2016 ◽  
Vol 24 ◽  
pp. S244
Author(s):  
Eloise Hudry ◽  
Jonathan Dashkoff ◽  
Paul Lerner ◽  
Shuko Takeda ◽  
Nhi Truong ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Types ◽  
Specific Cell ◽  
The Central Nervous System

scholarly journals Dynamic Role of Phospholipases A2 in Health and Diseases in the Central Nervous System

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2963
Author(s):  
Grace Y. Sun ◽  
Xue Geng ◽  
Tao Teng ◽  
Bo Yang ◽  
Michael K. Appenteng ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cellular Localization ◽  
Cell Types ◽  
Molecular Structures ◽  
Specific Cell ◽  
Phospholipases A2 ◽  
Cell Functions ◽  
The Central Nervous System

Phospholipids are major components in the lipid bilayer of cell membranes. These molecules are comprised of two acyl or alkyl groups and different phospho-base groups linked to the glycerol backbone. Over the years, substantial interest has focused on metabolism of phospholipids by phospholipases and the role of their metabolic products in mediating cell functions. The high levels of polyunsaturated fatty acids (PUFA) in the central nervous system (CNS) have led to studies centered on phospholipases A2 (PLA2s), enzymes responsible for cleaving the acyl groups at the sn-2 position of the phospholipids and resulting in production of PUFA and lysophospholipids. Among the many subtypes of PLA2s, studies have centered on three major types of PLA2s, namely, the calcium-dependent cytosolic cPLA2, the calcium-independent iPLA2 and the secretory sPLA2. These PLA2s are different in their molecular structures, cellular localization and, thus, production of lipid mediators with diverse functions. In the past, studies on specific role of PLA2 on cells in the CNS are limited, partly because of the complex cellular make-up of the nervous tissue. However, understanding of the molecular actions of these PLA2s have improved with recent advances in techniques for separation and isolation of specific cell types in the brain tissue as well as development of sensitive molecular tools for analyses of proteins and lipids. A major goal here is to summarize recent studies on the characteristics and dynamic roles of the three major types of PLA2s and their oxidative products towards brain health and neurological disorders.

scholarly journals Cell type-specific Pathways Associated with Diffuse Large B-cell Lymphoma Metastasis Related to Neuro-Diseases

2021 ◽  
Author(s):  
Ashmita Dey ◽  
Ujjwal Maulik
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Single Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cell Types ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Abstract Background: With the advancement of single-cell sequencing, it’s become rapid emergency to detect the cell-specific changes of Diffuse Large B-cell Lymphoma metastasis that leads to the central nervous system disorder. Results: In this study, single-cell RNA-seq of Peripheral blood mononuclear cell from a human sample is curated and cell types related to lymphocytes are identified. Subsequently, the potential markers of Diffuse Large B-cell Lymphoma are found. It is noticed that LEF1, TCF7 and CD79A/B markers of different cell types show an important role in this disease formation, progression and metastasis processes. To understand the impact of markers, associated pathways are studied in details by establishing a pathway semantic network. Moreover, this association validated the channel through which the pathways are triggered within the cell environment and resulted in metastasis. The connection between Diffuse Large B-cell Lymphoma metastasis and other central nervous system disorders is demonstrated by constructing a disease network. Conclusion: The study reveals how cell types are responsible for the pathway shifts. Furthermore, this information provides a cell-specific channel of triggering the progression of central nervous system diseases among Diffuse Large B-cell Lymphoma patients.

scholarly journals NG2 Glia: Novel Roles beyond Re-/Myelination

Neuroglia ◽  
2018 ◽  
Vol 1 (1) ◽  
pp. 151-175 ◽  
Author(s):  
Roberta Parolisi ◽  
Enrica Boda
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuronal Activity ◽  
Cell Types ◽  
Specific Cell ◽  
Transitional Stage ◽  
Cell Type ◽  
Functional Interactions ◽  
Cell Ablation ◽  
Novel Approaches

Neuron-glia antigen 2-expressing glial cells (NG2 glia) serve as oligodendrocyte progenitors during development and adulthood. However, recent studies have shown that these cells represent not only a transitional stage along the oligodendroglial lineage, but also constitute a specific cell type endowed with typical properties and functions. Namely, NG2 glia (or subsets of NG2 glia) establish physical and functional interactions with neurons and other central nervous system (CNS) cell types, that allow them to constantly monitor the surrounding neuropil. In addition to operating as sensors, NG2 glia have features that are expected for active modulators of neuronal activity, including the expression and release of a battery of neuromodulatory and neuroprotective factors. Consistently, cell ablation strategies targeting NG2 glia demonstrate that, beyond their role in myelination, these cells contribute to CNS homeostasis and development. In this review, we summarize and discuss the advancements achieved over recent years toward the understanding of such functions, and propose novel approaches for further investigations aimed at elucidating the multifaceted roles of NG2 glia.

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