scholarly journals Th2 Cytokine Modulates Herpesvirus Reactivation in a Cell Type Specific Manner

2020 ◽  
Author(s):  
Guoxun Wang ◽  
Christina Zarek ◽  
Tyron Chang ◽  
Lili Tao ◽  
Alexandria Lowe ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Types ◽  
Receptor Expression ◽  
Conditional Knockout ◽  
Interleukin 4 ◽  
Virus Reactivation ◽  
Cell Type ◽  
Viral Promoter ◽  
Murine Gammaherpesvirus ◽  
Cell Type Specific

AbstractGammaherpesviruses, such as Epstein-Barr virus (EBV), Kaposi’s sarcoma associated virus (KSHV), and murine γ-herpesvirus 68 (MHV68), establish latent infection in B cells, macrophages, and non-lymphoid cells, and can induce both lymphoid and non-lymphoid cancers. Research on these viruses has relied heavily on immortalized B cell and endothelial cell lines. Therefore, we know very little about the cell type specific regulation of virus infection. We have previously shown that treatment of MHV68-infected macrophages with the cytokine interleukin-4 (IL-4) or challenge of MHV68-infected mice with an IL-4-inducing parasite leads to virus reactivation. However, we do not know if all latent reservoirs of the virus, including B cells, reactivate the virus in response to IL-4. Here we used an in vivo approach to address the question of whether all latently infected cell types reactivate MHV68 in response to a particular stimulus. We found that IL-4 receptor expression on macrophages was required for IL-4 to induce virus reactivation, but that it was dispensable on B cells. We further demonstrated that the transcription factor, STAT6, which is downstream of the IL-4 receptor and binds a viral promoter in macrophages, did not bind to the viral promoter in B cells. These data suggest that stimuli that promote herpesvirus reactivation may only affect latent virus in particular cell types, but not in others.ImportanceHerpesviruses establish life-long quiescent infections in specific cells in the body, and only reactivate to produce infectious virus when precise signals induce them to do so. The signals that induce herpesvirus reactivation are often studied only in one particular cell type infected with the virus. However, herpesviruses establish latency in multiple cell types in their hosts. Using murine gammaherpesvirus-68 (MHV68) and conditional knockout mice, we examined the cell type specificity of a particular reactivation signal, interleukin-4 (IL-4). We found that IL-4 only induced herpesvirus reactivation from macrophages, but not from B cells. This work indicates that regulation of virus latency and reactivation is cell type specific. This has important implications for therapies aimed at either promoting or inhibiting reactivation for the control or elimination of chronic viral infections.

scholarly journals Th2 Cytokine Modulates Herpesvirus Reactivation in a Cell Type Specific Manner

2021 ◽  
Author(s):  
Guoxun Wang ◽  
Christina Zarek ◽  
Tyron Chang ◽  
Lili Tao ◽  
Alexandria Lowe ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Types ◽  
The Body ◽  
Receptor Expression ◽  
Conditional Knockout ◽  
Interleukin 4 ◽  
Virus Reactivation ◽  
Cell Type ◽  
Murine Gammaherpesvirus ◽  
Cell Type Specific

Gammaherpesviruses, such as Epstein-Barr virus (EBV), Kaposi’s sarcoma associated virus (KSHV), and murine γ-herpesvirus 68 (MHV68), establish latent infection in B cells, macrophages, and non-lymphoid cells, and can induce both lymphoid and non-lymphoid cancers. Research on these viruses has relied heavily on immortalized B cell and endothelial cell lines. Therefore, we know very little about the cell type specific regulation of virus infection. We have previously shown that treatment of MHV68-infected macrophages with the cytokine interleukin-4 (IL-4) or challenge of MHV68-infected mice with an IL-4-inducing parasite leads to virus reactivation. However, we do not know if all latent reservoirs of the virus, including B cells, reactivate the virus in response to IL-4. Here we used an in vivo approach to address the question of whether all latently infected cell types reactivate MHV68 in response to a particular stimulus. We found that IL-4 receptor expression on macrophages was required for IL-4 to induce virus reactivation, but that it was dispensable on B cells. We further demonstrated that the transcription factor, STAT6, which is downstream of the IL-4 receptor and binds virus gene 50 N4/N5 promoter in macrophages, did not bind to the virus gene 50 N4/N5 promoter in B cells. These data suggest that stimuli that promote herpesvirus reactivation may only affect latent virus in particular cell types, but not in others. Importance Herpesviruses establish life-long quiescent infections in specific cells in the body, and only reactivate to produce infectious virus when precise signals induce them to do so. The signals that induce herpesvirus reactivation are often studied only in one particular cell type infected with the virus. However, herpesviruses establish latency in multiple cell types in their hosts. Using murine gammaherpesvirus-68 (MHV68) and conditional knockout mice, we examined the cell type specificity of a particular reactivation signal, interleukin-4 (IL-4). We found that IL-4 only induced herpesvirus reactivation from macrophages, but not from B cells. This work indicates that regulation of virus latency and reactivation is cell type specific. This has important implications for therapies aimed at either promoting or inhibiting reactivation for the control or elimination of chronic viral infections.

scholarly journals Cell Specific Dopamine Modulation of the Transient Potassium Current in the Pyloric Network by the Canonical D1 Receptor Signal Transduction Cascade

2010 ◽  
Vol 104 (2) ◽  
pp. 873-884 ◽  
Author(s):  
Hongmei Zhang ◽  
Edmund W. Rodgers ◽  
Wulf-Dieter C. Krenz ◽  
Merry C. Clark ◽  
Deborah J. Baro
Keyword(s):  
Potassium Current ◽  
Expression System ◽  
Expression Patterns ◽  
Motor Pattern ◽  
Cell Types ◽  
Receptor Expression ◽  
Intracellular Camp ◽  
Cell Type ◽  
Pyloric Network ◽  
Cell Type Specific

Dopamine (DA) modifies the motor pattern generated by the pyloric network in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus , by directly acting on each of the circuit neurons. The 14 pyloric neurons fall into six cell types, and DA actions are cell type specific. The transient potassium current mediated by shal channels ( IA) is a common target of DA modulation in most cell types. DA shifts the voltage dependence of IA in opposing directions in pyloric dilator (PD) versus lateral pyloric (LP) neurons. The mechanism(s) underpinning cell-type specific DA modulation of IA is unknown. DA receptors (DARs) can be classified as type 1 (D1R) or type 2 (D2R). D1Rs and D2Rs are known to increase and decrease intracellular cAMP concentrations, respectively. We hypothesized that the opposing DA effects on PD and LP IA were due to differences in DAR expression patterns. In the present study, we found that LP expressed somatodendritic D1Rs that were concentrated near synapses but did not express D2Rs. Consistently, DA modulation of LP IA was mediated by a Gs-adenylyl cyclase-cAMP-protein kinase A pathway. Additionally, we defined antagonists for lobster D1Rs (flupenthixol) and D2Rs (metoclopramide) in a heterologous expression system and showed that DA modulation of LP IA was blocked by flupenthixol but not by metoclopramide. We previously showed that PD neurons express D2Rs, but not D1Rs, thus supporting the idea that cell specific effects of DA on IA are due to differences in receptor expression.

scholarly journals Systematic and Cell Type-Specific Telomere Length Changes in Subsets of Lymphocytes

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Jue Lin ◽  
Joshua Cheon ◽  
Rashida Brown ◽  
Michael Coccia ◽  
Eli Puterman ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Telomere Length ◽  
Cell Types ◽  
Cell Type ◽  
Peripheral Blood Mononuclear ◽  
Potential Biomarker ◽  
Cell Type Specific ◽  
Length Changes

Telomeres, the protective DNA-protein complexes at the ends of linear chromosomes, are important for genome stability. Leukocyte or peripheral blood mononuclear cell (PBMC) telomere length is a potential biomarker for human aging that integrates genetic, environmental, and lifestyle factors and is associated with mortality and risks for major diseases. However, only a limited number of studies have examined longitudinal changes of telomere length and few have reported data on sorted circulating immune cells. We examined the average telomere length (TL) in CD4+, CD8+CD28+, and CD8+CD28− T cells, B cells, and PBMCs, cross-sectionally and longitudinally, in a cohort of premenopausal women. We report that TL changes over 18 months were correlated among these three T cell types within the same participant. Additionally, PBMC TL change was also correlated with those of all three T cell types, and B cells. The rate of shortening for B cells was significantly greater than for the three T cell types. CD8+CD28− cells, despite having the shortest TL, showed significantly more rapid attrition when compared to CD8+CD28+ T cells. These results suggest systematically coordinated, yet cell type-specific responses to factors and pathways contribute to telomere length regulation.

scholarly journals Cell Type–Specific Decomposition of Gingival Tissue Transcriptomes

2021 ◽  
pp. 002203452097961
Author(s):  
F. Momen-Heravi ◽  
R.A. Friedman ◽  
S. Albeshri ◽  
A. Sawle ◽  
M. Kebschull ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cells ◽  
Epithelial Cells ◽  
Differentially Expressed Genes ◽  
Cell Types ◽  
Differentially Expressed ◽  
Gingival Tissue ◽  
Cell Type ◽  
Data Set ◽  
Cell Type Specific

Genome-wide transcriptomic analyses in whole tissues reflect the aggregate gene expression in heterogeneous cell populations comprising resident and migratory cells, and they are unable to identify cell type–specific information. We used a computational method (population-specific expression analysis [PSEA]) to decompose gene expression in gingival tissues into cell type–specific signatures for 8 cell types (epithelial cells, fibroblasts, endothelial cells, neutrophils, monocytes/macrophages, plasma cells, T cells, and B cells). We used a gene expression data set generated using microarrays from 120 persons (310 tissue samples; 241 periodontitis affected and 69 healthy). Decomposition of the whole-tissue transcriptomes identified differentially expressed genes in each of the cell types, which mapped to biologically relevant pathways, including dysregulation of Th17 cell differentiation, AGE-RAGE signaling, and epithelial-mesenchymal transition in epithelial cells. We validated selected PSEA-predicted, differentially expressed genes in purified gingival epithelial cells and B cells from an unrelated cohort ( n = 15 persons), each of whom contributed with 1 periodontitis-affected and 1 healthy gingival tissue sample. Differential expression of these genes by quantitative reverse transcription polymerase chain reaction corroborated the PSEA predictions and pointed to dysregulation of biologically important pathways in periodontitis. Collectively, our results demonstrate the robustness of the PSEA in the decomposition of gingival tissue transcriptomes and its ability to identify differentially regulated transcripts in particular cellular constituents. These genes may serve as candidates for further investigation with respect to their roles in the pathogenesis of periodontitis.

scholarly journals Connectivity characterization of the mouse basolateral amygdalar complex

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Houri Hintiryan ◽  
Ian Bowman ◽  
David L. Johnson ◽  
Laura Korobkova ◽  
Muye Zhu ◽  
...  
Keyword(s):  
Granular Cell ◽  
Cell Types ◽  
Projection Neurons ◽  
Cell Type ◽  
Connectivity Map ◽  
Analysis Techniques ◽  
Domain Specific ◽  
Cell Type Specific ◽  
Unique Domain

AbstractThe basolateral amygdalar complex (BLA) is implicated in behaviors ranging from fear acquisition to addiction. Optogenetic methods have enabled the association of circuit-specific functions to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. Here, we apply machine-learning based computational and informatics analysis techniques to the results of circuit-tracing experiments to create a foundational, comprehensive BLA connectivity map. The analyses identify three distinct domains within the anterior BLA (BLAa) that house target-specific projection neurons with distinguishable morphological features. We identify brain-wide targets of projection neurons in the three BLAa domains, as well as in the posterior BLA, ventral BLA, posterior basomedial, and lateral amygdalar nuclei. Inputs to each nucleus also are identified via retrograde tracing. The data suggests that connectionally unique, domain-specific BLAa neurons are associated with distinct behavior networks.

scholarly journals Shisa6 mediates cell-type specific regulation of depression in the nucleus accumbens

2021 ◽  
Author(s):  
Hee-Dae Kim ◽  
Jing Wei ◽  
Tanessa Call ◽  
Nicole Teru Quintus ◽  
Alexander J. Summers ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Current Treatment ◽  
Specific Cell ◽  
Excitatory Synapses ◽  
Cell Type ◽  
Cell Type Specific ◽  
Specific Regulation ◽  
Circuit Function

AbstractDepression is the leading cause of disability and produces enormous health and economic burdens. Current treatment approaches for depression are largely ineffective and leave more than 50% of patients symptomatic, mainly because of non-selective and broad action of antidepressants. Thus, there is an urgent need to design and develop novel therapeutics to treat depression. Given the heterogeneity and complexity of the brain, identification of molecular mechanisms within specific cell-types responsible for producing depression-like behaviors will advance development of therapies. In the reward circuitry, the nucleus accumbens (NAc) is a key brain region of depression pathophysiology, possibly based on differential activity of D1- or D2- medium spiny neurons (MSNs). Here we report a circuit- and cell-type specific molecular target for depression, Shisa6, recently defined as an AMPAR component, which is increased only in D1-MSNs in the NAc of susceptible mice. Using the Ribotag approach, we dissected the transcriptional profile of D1- and D2-MSNs by RNA sequencing following a mouse model of depression, chronic social defeat stress (CSDS). Bioinformatic analyses identified cell-type specific genes that may contribute to the pathogenesis of depression, including Shisa6. We found selective optogenetic activation of the ventral tegmental area (VTA) to NAc circuit increases Shisa6 expression in D1-MSNs. Shisa6 is specifically located in excitatory synapses of D1-MSNs and increases excitability of neurons, which promotes anxiety- and depression-like behaviors in mice. Cell-type and circuit-specific action of Shisa6, which directly modulates excitatory synapses that convey aversive information, identifies the protein as a potential rapid-antidepressant target for aberrant circuit function in depression.

scholarly journals Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
John A. Halsall ◽  
Simon Andrews ◽  
Felix Krueger ◽  
Charlotte E. Rutledge ◽  
Gabriella Ficz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Histone Modifications ◽  
Expression Patterns ◽  
Cell Types ◽  
Cell Type ◽  
Bar Code ◽  
Genes Encoding ◽  
Cell Type Specific ◽  
Rolling Windows

AbstractChromatin configuration influences gene expression in eukaryotes at multiple levels, from individual nucleosomes to chromatin domains several Mb long. Post-translational modifications (PTM) of core histones seem to be involved in chromatin structural transitions, but how remains unclear. To explore this, we used ChIP-seq and two cell types, HeLa and lymphoblastoid (LCL), to define how changes in chromatin packaging through the cell cycle influence the distributions of three transcription-associated histone modifications, H3K9ac, H3K4me3 and H3K27me3. We show that chromosome regions (bands) of 10–50 Mb, detectable by immunofluorescence microscopy of metaphase (M) chromosomes, are also present in G1 and G2. They comprise 1–5 Mb sub-bands that differ between HeLa and LCL but remain consistent through the cell cycle. The same sub-bands are defined by H3K9ac and H3K4me3, while H3K27me3 spreads more widely. We found little change between cell cycle phases, whether compared by 5 Kb rolling windows or when analysis was restricted to functional elements such as transcription start sites and topologically associating domains. Only a small number of genes showed cell-cycle related changes: at genes encoding proteins involved in mitosis, H3K9 became highly acetylated in G2M, possibly because of ongoing transcription. In conclusion, modified histone isoforms H3K9ac, H3K4me3 and H3K27me3 exhibit a characteristic genomic distribution at resolutions of 1 Mb and below that differs between HeLa and lymphoblastoid cells but remains remarkably consistent through the cell cycle. We suggest that this cell-type-specific chromosomal bar-code is part of a homeostatic mechanism by which cells retain their characteristic gene expression patterns, and hence their identity, through multiple mitoses.

scholarly journals An analytical method for the identification of cell type-specific disease gene modules

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jinting Guan ◽  
Yiping Lin ◽  
Yang Wang ◽  
Junchao Gao ◽  
Guoli Ji
Keyword(s):  
Disease Gene ◽  
Gene Interaction ◽  
Cell Types ◽  
Autism Spectrum ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Disease ◽  
Cell Type Specific ◽  
Gene Modules ◽  
Disease Associated Genes

Abstract Background Genome-wide association studies have identified genetic variants associated with the risk of brain-related diseases, such as neurological and psychiatric disorders, while the causal variants and the specific vulnerable cell types are often needed to be studied. Many disease-associated genes are expressed in multiple cell types of human brains, while the pathologic variants affect primarily specific cell types. We hypothesize a model in which what determines the manifestation of a disease in a cell type is the presence of disease module comprised of disease-associated genes, instead of individual genes. Therefore, it is essential to identify the presence/absence of disease gene modules in cells. Methods To characterize the cell type-specificity of brain-related diseases, we construct human brain cell type-specific gene interaction networks integrating human brain nucleus gene expression data with a referenced tissue-specific gene interaction network. Then from the cell type-specific gene interaction networks, we identify significant cell type-specific disease gene modules by performing statistical tests. Results Between neurons and glia cells, the constructed cell type-specific gene networks and their gene functions are distinct. Then we identify cell type-specific disease gene modules associated with autism spectrum disorder and find that different gene modules are formed and distinct gene functions may be dysregulated in different cells. We also study the similarity and dissimilarity in cell type-specific disease gene modules among autism spectrum disorder, schizophrenia and bipolar disorder. The functions of neurons-specific disease gene modules are associated with synapse for all three diseases, while those in glia cells are different. To facilitate the use of our method, we develop an R package, CtsDGM, for the identification of cell type-specific disease gene modules. Conclusions The results support our hypothesis that a disease manifests itself in a cell type through forming a statistically significant disease gene module. The identification of cell type-specific disease gene modules can promote the development of more targeted biomarkers and treatments for the disease. Our method can be applied for depicting the cell type heterogeneity of a given disease, and also for studying the similarity and dissimilarity between different disorders, providing new insights into the molecular mechanisms underlying the pathogenesis and progression of diseases.

Cytoplasmic, nuclear, membrane-bound and secreted [35S]methionine-labelled polypeptide pattern in differentiating fibroblast stem cells in vitro

1989 ◽  
Vol 92 (2) ◽  
pp. 231-239
Author(s):  
P.I. Francz ◽  
K. Bayreuther ◽  
H.P. Rodemann
Keyword(s):  
Protein Fraction ◽  
Fibroblast Cell ◽  
Cell Types ◽  
Specific Marker ◽  
Human Skin Fibroblast ◽  
Nuclear Fraction ◽  
Cell Type ◽  
Marker Proteins ◽  
Cell Type Specific ◽  
Membrane Bound

Methods for the selective enrichment of various subpopulations of the human skin fibroblast cell line HH-8 have been developed. These methods permit the selection of homogeneous populations of the three mitotic fibroblast cell types MF I, II and III, and the four postmitotic cell types PMF IV, V, VI and VII. These seven cell types exhibit differentiation-dependent and cell-type-specific patterns of [35S]methionine-labelled polypeptides in total soluble cytoplasmic and nuclear proteins, also in membrane-bound proteins, and in secreted proteins. In the differentiation sequence MF II-MF III-PMF IV - PMF V - PMF VI 14 cell-type-specific marker proteins have been found in the cytoplasmic and nuclear fraction, also 24 cell-type-specific marker proteins have been found in the membrane-bound protein fraction, and 11 cell-type-specific marker proteins in the secreted protein fraction. Markers in spontaneously arising and experimentally selected or induced populations of a single fibroblast cell type were found to be identical.

Sign in / Sign up

Export Citation Format

Share Document