scholarly journals Chemical and Light Inducible Epigenome Editing

2020 ◽  
Vol 21 (3) ◽  
pp. 998
Author(s):  
Weiye Zhao ◽  
Yufan Wang ◽  
Fu-Sen Liang
Keyword(s):  
Small Molecules ◽  
Expression Patterns ◽  
Cell Types ◽  
Epigenome Editing ◽  
Specific Targeting ◽  
Conditional Control ◽  
Cellular Behaviors ◽  
Different Cell Types ◽  
Kinetics Of ◽  
Epigenetic Research

The epigenome defines the unique gene expression patterns and resulting cellular behaviors in different cell types. Epigenome dysregulation has been directly linked to various human diseases. Epigenome editing enabling genome locus-specific targeting of epigenome modifiers to directly alter specific local epigenome modifications offers a revolutionary tool for mechanistic studies in epigenome regulation as well as the development of novel epigenome therapies. Inducible and reversible epigenome editing provides unique temporal control critical for understanding the dynamics and kinetics of epigenome regulation. This review summarizes the progress in the development of spatiotemporal-specific tools using small molecules or light as inducers to achieve the conditional control of epigenome editing and their applications in epigenetic research.

scholarly journals Phosphorylation and internalization of gp130 occur after IL-6 activation of Jak2 kinase in hepatocytes.

1994 ◽  
Vol 5 (7) ◽  
pp. 819-828 ◽  
Author(s):  
Y Wang ◽  
G M Fuller
Keyword(s):  
Protein Synthesis ◽  
Cell Surface ◽  
De Novo ◽  
Cell Types ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Protein Synthesis Inhibitors ◽  
Different Cell Types ◽  
Kinetics Of

Recent evidence has shown that members of the Jak kinase family are activated after IL-6 binds to its receptor complex, leading to a tyrosine phosphorylation of gp130, the IL-6 signal-transducing subunit. The different members of the IL-6 cytokine subfamily induce distinct patterns of Jak-Tyk phosphorylation in different cell types. Using monospecific antibodies to gp130, Jak2 kinase, and phosphotyrosine, we investigated the kinetics of IL-6 stimulation of members of this pathway in primary hepatocytes. Our findings show that Jak 2 is maximally activated within 2 min of exposure to IL-6, followed by gp130 phosphorylation that reaches its peak in another 2 min then declines to basal level by 60 min. In vitro phosphorylation experiments show that activated Jak 2 is able to phosphorylate both native gp130 and a fusion peptide containing its cytoplasmic domain, demonstrating gp130 is a direct substrate of Jak 2 kinase. Experiments designed to explore the cell surface expression of gp130 show that > or = 2 h are required to get a second round of phosphorylation after the addition of more cytokines. This finding suggests that activated gp130 is internalized from the cell surface after IL-6 stimulation. Additional experiments using protein synthesis inhibitors reveal that new protein synthesis is required to get a second cycle of gp130 phosphorylation indicating gp130 must be synthesized de novo and inserted into the membrane. These findings provide strong evidence that down regulation of the IL-6 signal in hepatocytes involves the internalization and cytosol degradation of gp130.

scholarly journals Global Analysis of Cell Type-Specific Gene Expression

2003 ◽  
Vol 4 (2) ◽  
pp. 208-215 ◽  
Author(s):  
David W. Galbraith
Keyword(s):  
Gene Expression ◽  
Fluorescent Protein ◽  
Global Analysis ◽  
Expression Patterns ◽  
Three Dimensional ◽  
Global Gene Expression ◽  
Cell Types ◽  
Reasonable Assumption ◽  
Specific Gene ◽  
Different Cell Types

The tissues and organs of multicellular eukaryotes are frequently observed to comprise complex three-dimensional interspersions of different cell types. It is a reasonable assumption that different global patterns of gene expression are found within these different cell types. This review outlines general experimental strategies designed to characterize these global gene expression patterns, based on a combination of methods of transgenic fluorescent protein (FP) expression and targeting, of flow cytometry and sorting and of high-throughput gene expression analysis.

scholarly journals A genetic, genomic, and computational resource for exploring neural circuit function

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Fred P Davis ◽  
Aljoscha Nern ◽  
Serge Picard ◽  
Michael B Reiser ◽  
Gerald M Rubin ◽  
...  
Keyword(s):  
Neural Circuits ◽  
Neural Circuit ◽  
Individual Cell ◽  
Probabilistic Method ◽  
Expression Patterns ◽  
Cell Types ◽  
Receptor Expression ◽  
Generating Functional ◽  
Circuit Function ◽  
Different Cell Types

The anatomy of many neural circuits is being characterized with increasing resolution, but their molecular properties remain mostly unknown. Here, we characterize gene expression patterns in distinct neural cell types of the Drosophila visual system using genetic lines to access individual cell types, the TAPIN-seq method to measure their transcriptomes, and a probabilistic method to interpret these measurements. We used these tools to build a resource of high-resolution transcriptomes for 100 driver lines covering 67 cell types, available at http://www.opticlobe.com. Combining these transcriptomes with recently reported connectomes helps characterize how information is transmitted and processed across a range of scales, from individual synapses to circuit pathways. We describe examples that include identifying neurotransmitters, including cases of apparent co-release, generating functional hypotheses based on receptor expression, as well as identifying strong commonalities between different cell types.

scholarly journals A genetic, genomic, and computational resource for exploring neural circuit function

2018 ◽  
Author(s):  
Fred P. Davis ◽  
Aljoscha Nern ◽  
Serge Picard ◽  
Michael B. Reiser ◽  
Gerald M. Rubin ◽  
...  
Keyword(s):  
Neural Circuit ◽  
Affinity Purification ◽  
Probabilistic Method ◽  
Expression Patterns ◽  
Cell Types ◽  
Receptor Expression ◽  
List Type ◽  
Visual Neurons ◽  
Circuit Function ◽  
Different Cell Types

AbstractThe anatomy of many neural circuits is being characterized with increasing resolution, but their molecular properties remain mostly unknown. Here, we characterize gene expression patterns in distinct neural cell types of the Drosophila visual system using genetic lines to access individual cell types, the TAPIN-seq method to measure their transcriptomes, and a probabilistic method to interpret these measurements. We used these tools to build a resource of high-resolution transcriptomes for 100 driver lines covering 67 cell types, available at http://www.opticlobe.com. Combining these transcriptomes with recently reported connectomes helps characterize how information is transmitted and processed across a range of scales, from individual synapses to circuit pathways. We describe examples that include identifying neurotransmitters, including cases of co-release, generating functional hypotheses based on receptor expression, as well as identifying strong commonalities between different cell types.HighlightsTranscriptomes reveal transmitters and receptors expressed in Drosophila visual neuronsTandem affinity purification of intact nuclei (TAPIN) enables neuronal genomicsTAPIN-seq and genetic drivers establish transcriptomes of 67 Drosophila cell typesProbabilistic modeling simplifies interpretation of large transcriptome catalogs

scholarly journals Efficiencies and kinetics of infection in different cell types/lines by African and Asian strains of Zika virus

2018 ◽  
Vol 91 (2) ◽  
pp. 179-189 ◽  
Author(s):  
Suzane Ramos da Silva ◽  
Fan Cheng ◽  
I‐Chueh Huang ◽  
Jae U. Jung ◽  
Shou‐Jiang Gao
Keyword(s):  
Zika Virus ◽  
Cell Types ◽  
Different Cell Types ◽  
Kinetics Of

Energetics of muscle contraction: the whole is less than the sum of its parts

2002 ◽  
Vol 30 (2) ◽  
pp. 227-231 ◽  
Author(s):  
M. J. Kushmerick ◽  
K. E. Conley
Keyword(s):  
Oxidative Phosphorylation ◽  
Supply And Demand ◽  
Lactate Production ◽  
Cell Types ◽  
Individual Values ◽  
Muscle Energetics ◽  
Modular Units ◽  
Small Set ◽  
Different Cell Types ◽  
Kinetics Of

Understanding muscle energetics is a problem in optimizing supply of ATP to the demands of ATPases. The complexity of reactions and their fluxes to achieve this balance is greatly reduced by recognizing constraints imposed by the integration of common metabolites at fixed stoichiometry among modular units. ATPase is driven externally. Oxidative phosphorylation and glycogenolysis are the suppliers. We focus on their regulation which involves different controls, but reduces to two principles that enable facile experimental analysis of the supply and demand fluxes. The ratio of concentration of phospho-creatine (PCr) to ATP, not their individual values, sets the range of achievable concentrations of ADP in resting and active muscle (at fixed pH) in different cell types. This principle defines the fraction of available flux of oxidative phosphorylation utilized (at fixed enzyme activities). Then the kinetics of PCr recovery defines the kinetics of oxygen supply and substrate utilization. The second principle is the constancy of PCr and H+ (lactate) production by glycogenolysis due to the coupling of ATPase and glycolysis. This principle enables glycogenolytic flux to be measured from intracellular proton loads. Further simplification occurs because the magnitude of the interacting fluxes and metabolite concentrations are specified within narrow limits when both the resting and active fluxes are quantified. Thus there is a small set of rules for assessing and understanding the thermodynamics and kinetics of muscle energetics.

scholarly journals Carboxyfluorescein Diacetate Succinimidyl Ester Fluorescent Dye for Cell Labeling

2005 ◽  
Vol 37 (6) ◽  
pp. 379-385 ◽  
Author(s):  
Xiao-Qi Wang ◽  
Xiu-Mei Duan ◽  
Li-Hua Liu ◽  
Yan-Qiu Fang ◽  
Yan Tan
Keyword(s):  
Death Rate ◽  
Cell Types ◽  
Fluorescent Dye ◽  
Optimal Concentration ◽  
Cell Labeling ◽  
Cell Death Rate ◽  
Succinimidyl Ester ◽  
Different Cell Types ◽  
Kinetics Of ◽  
Diacetate Succinimidyl

Abstract Our objective was to study the properties of the carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) and the methodology of cell labeling using CFDA-SE fluorescent dye. First, we analyzed the kinetics of CFDA-SE fluorescent dye intensity over time. Second, we determined the optimal concentration of CFDA-SE fluorescent dye for cell labeling. Third, we tested the toxicity of CFDA-SE fluorescent dye on labeled cells. Finally, we determined the optimal staining time of CFDA-SE fluorescent dye for cell labeling. The results show that the optimal concentration of CFDA-SE fluorescent dye for cell labeling varies according to different cell types. CFDA-SE fluorescent dye is non-toxic to cells as the cell death rate caused by CFDASE labeling is below 5%. The optimal cell labeling time was determined to be 8 min of incubation with CFDA-SE fluorescent dye. We concluded that the advantages of using CFDA-SE fluorescent dye for cell labeling are as follows: (1) the binding of CFDA-SE fluorescent dye to cells is stable; (2) CFDA-SE fluorescent dye is not toxic and does not modify the viability of labeled cells; and (3) CFDA-SE fluorescent dye is a suitable fluorochrome for cell labeling.

scholarly journals GLI ESOSOMI NELLA COMUNICAZIONE CELLULA-CELLULA

2020 ◽  
Author(s):  
Stefania Raimondo
Keyword(s):  
Small Molecules ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Cell Types ◽  
Cell Contact ◽  
Bioactive Lipids ◽  
Pathological Conditions ◽  
Extracellular Matrix Components ◽  
Different Cell Types ◽  
Cell Cell

Cell to cell communication is essential for the coordination and proper organization of different cell types in multicellular systems. Cells exchange information through a multitude of mechanisms such as secreted growth factors and chemokines, small molecules (peptides, ions, bioactive lipids and nucleotides), cell-cell contact and the secretion of extracellular matrix components. Over the last few years a new and sophisticated mechanism of cell-cell communication based on extracellular vesicles has been described. Extracellular vesicles are specialized vesicles released in the extracellular space by most of cell types, under physiological and pathological conditions. Among different extracellular vesicles subtypes, exosomes (30-100 nm) have recently received most of the attention do to their ability to be messenger in intercellular communication.

scholarly journals Heterogeneity of Transcription Factor binding specificity models within and across cell lines

2015 ◽  
Author(s):  
Mahfuza Sharmin ◽  
Hector Corrada Bravo ◽  
Sridhar S. Hannenhalli
Keyword(s):  
Expression Patterns ◽  
Specific Interaction ◽  
Cell Types ◽  
Cell Type ◽  
Binding Interaction ◽  
Interaction Partners ◽  
A Cell ◽  
Cell Type Specific ◽  
Different Cell Types

Complex gene expression patterns are mediated by binding of transcription factors (TF) to specific genomic loci. The in vivo occupancy of a TF is, in large part, determined by the TFs DNA binding interaction partners, motivating genomic context based models of TF occupancy. However, the approaches thus far have assumed a uniform binding model to explain genome wide bound sites for a TF in a cell-type and as such heterogeneity of TF occupancy models, and the extent to which binding rules underlying a TFs occupancy are shared across cell types, has not been investigated. Here, we develop an ensemble based approach (TRISECT) to identify heterogeneous binding rules of cell-type specific TF occupancy and analyze the inter-cell-type sharing of such rules. Comprehensive analysis of 23 TFs, each with ChIP-Seq data in 4-12 cell-types, shows that by explicitly capturing the heterogeneity of binding rules, TRISECT accurately identifies in vivo TF occupancy (93%) substantially improving upon previous methods. Importantly, many of the binding rules derived from individual cell-types are shared across cell-types and reveal distinct yet functionally coherent putative target genes in different cell-types. Closer inspection of the predicted cell-type-specific interaction partners provides insights into context-specific functional landscape of a TF. Together, our novel ensemble-based approach reveals, for the first time, a widespread heterogeneity of binding rules, comprising interaction partners within a cell-type, many of which nevertheless transcend cell-types. Notably, the putative targets of shared binding rules in different cell-types, while distinct, exhibit significant functional coherence.

scholarly journals Potential Networks of Nitrogen-Phosphorus-Potassium Channels and Transporters in Arabidopsis Roots at a Single Cell Resolution

2021 ◽  
Vol 12 ◽  
Author(s):  
Dhondup Lhamo ◽  
Sheng Luan
Keyword(s):  
Single Cell ◽  
Expression Patterns ◽  
Cell Types ◽  
Long Distance ◽  
Specific Expression ◽  
Root Cells ◽  
Long Distance Transport ◽  
Npk Uptake ◽  
Transcriptomics Data ◽  
Different Cell Types

Nitrogen (N), phosphorus (P), and potassium (K) are three major macronutrients essential for plant life. These nutrients are acquired and transported by several large families of transporters expressed in plant roots. However, it remains largely unknown how these transporters are distributed in different cell-types that work together to transfer the nutrients from the soil to different layers of root cells and eventually reach vasculature for massive flow. Using the single cell transcriptomics data from Arabidopsis roots, we profiled the transcriptional patterns of putative nutrient transporters in different root cell-types. Such analyses identified a number of uncharacterized NPK transporters expressed in the root epidermis to mediate NPK uptake and distribution to the adjacent cells. Some transport genes showed cortex- and endodermis-specific expression to direct the nutrient flow toward the vasculature. For long-distance transport, a variety of transporters were shown to express and potentially function in the xylem and phloem. In the context of subcellular distribution of mineral nutrients, the NPK transporters at subcellular compartments were often found to show ubiquitous expression patterns, which suggests function in house-keeping processes. Overall, these single cell transcriptomic analyses provide working models of nutrient transport from the epidermis across the cortex to the vasculature, which can be further tested experimentally in the future.

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