scholarly journals Bridging the gap between transcriptome and connectome

2018 ◽  
Author(s):  
Alex Fornito ◽  
Aurina Arnatkeviciute ◽  
Ben Fulcher
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Transcriptional Activity ◽  
Functional Specialization ◽  
Spatial Patterning ◽  
Molecular Function ◽  
Spatial Gradients ◽  
Diverse Species ◽  
Health And Disease ◽  
And Function

The recent construction of brain-wide gene expression atlases, which measure the transcriptional activity of thousands of genes in many different anatomical locations, has made it possible to connect spatial variations in gene expression to distributed properties of connectome structure and function. These analyses have revealed that spatial patterning of gene expression and neuronal connectivity are closely linked, following broad spatial gradients that track regional variations in microcircuitry, inter-regional connectivity and functional specialization. Superimposed on these gradients are more specific associations between gene expression and connectome topology that appear conserved across diverse species and resolution scales. These findings highlight the utility of brain-wide gene expression atlases for bridging the gap between molecular function and large-scale connectome organization in health and disease.

Neural system-enriched gene expression: relationship to biological pathways and neurological diseases

2004 ◽  
Vol 18 (2) ◽  
pp. 167-183 ◽  
Author(s):  
Jianhua Zhang ◽  
Amy Moseley ◽  
Anil G. Jegga ◽  
Ashima Gupta ◽  
David P. Witte ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Intracellular Signaling ◽  
Large Scale ◽  
Expression Profiles ◽  
Gene List ◽  
Structure And Function ◽  
System Structure ◽  
Psychiatric Disease ◽  
And Function

To understand the commitment of the genome to nervous system differentiation and function, we sought to compare nervous system gene expression to that of a wide variety of other tissues by gene expression database construction and mining. Gene expression profiles of 10 different adult nervous tissues were compared with that of 72 other tissues. Using ANOVA, we identified 1,361 genes whose expression was higher in the nervous system than other organs and, separately, 600 genes whose expression was at least threefold higher in one or more regions of the nervous system compared with their median expression across all organs. Of the 600 genes, 381 overlapped with the 1,361-gene list. Limited in situ gene expression analysis confirmed that identified genes did represent nervous system-enriched gene expression, and we therefore sought to evaluate the validity and significance of these top-ranked nervous system genes using known gene literature and gene ontology categorization criteria. Diverse functional categories were present in the 381 genes, including genes involved in intracellular signaling, cytoskeleton structure and function, enzymes, RNA metabolism and transcription, membrane proteins, as well as cell differentiation, death, proliferation, and division. We searched existing public sites and identified 110 known genes related to mental retardation, neurological disease, and neurodegeneration. Twenty-one of the 381 genes were within the 110-gene list, compared with a random expectation of 5. This suggests that the 381 genes provide a candidate set for further analyses in neurological and psychiatric disease studies and that as a field, we are as yet, far from a large-scale understanding of the genes that are critical for nervous system structure and function. Together, our data indicate the power of profiling an individual biologic system in a multisystem context to gain insight into the genomic basis of its structure and function.

scholarly journals A Potential of microRNAs for High-Content Screening

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Andrius Serva ◽  
Christoph Claas ◽  
Vytaute Starkuviene
Keyword(s):  
Large Scale ◽  
Cellular Processes ◽  
Comprehensive Knowledge ◽  
Functional Models ◽  
Rapid Accumulation ◽  
Health And Disease ◽  
Temporal And Spatial ◽  
And Function ◽  
Functional Analyses ◽  
Immense Potential

In the last years miRNAs have increasingly been recognised as potent posttranscriptional regulators of gene expression. Possibly, miRNAs exert their action on virtually any biological process by simultaneous regulation of numerous genes. The importance of miRNA-based regulation in health and disease has inspired research to investigate diverse aspects of miRNA origin, biogenesis, and function. Despite the recent rapid accumulation of experimental data, and the emergence of functional models, the complexity of miRNA-based regulation is still far from being well understood. In particular, we lack comprehensive knowledge as to which cellular processes are regulated by which miRNAs, and, furthermore, how temporal and spatial interactions of miRNAs to their targets occur. Results from large-scale functional analyses have immense potential to address these questions. In this review, we discuss the latest progress in application of high-content and high-throughput functional analysis for the systematic elucidation of the biological roles of miRNAs.

scholarly journals An improved CRISPR/dCas9 interference tool for neuronal gene suppression

2020 ◽  
Author(s):  
Corey G. Duke ◽  
Svitlana V. Bach ◽  
Jasmin S. Revanna ◽  
Faraz A. Sultan ◽  
Nicholas T. Southern ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Repression ◽  
Expression System ◽  
Genetic Material ◽  
Gene Promoters ◽  
Disease States ◽  
Transcriptional Inhibition ◽  
Health And Disease ◽  
Neuronal Systems ◽  
And Function

The expression of genetic material governs brain development, differentiation, and function, and targeted manipulation of gene expression is required to understand contributions of gene function to health and disease states. Although recent improvements in CRISPR/dCas9 interference (CRISPRi) technology have enabled targeted transcriptional repression at selected genomic sites, integrating these techniques for use in non-dividing neuronal systems remains challenging. Previously, we optimized a dual lentivirus expression system to express CRISPR-based activation machinery in post-mitotic neurons. Here we used a similar strategy to adapt an improved dCas9-KRAB-MeCP2 repression system for robust transcriptional inhibition in neurons. We find that lentiviral delivery of a dCas9-KRAB-MeCP2 construct driven by the neuron-selective promoter human synapsin 1 enabled transgene expression in primary rat neurons. Next, we demonstrate transcriptional repression using CRISPR sgRNAs targeting diverse gene promoters, and show superiority of this system in neurons compared to existing RNA interference methods for robust transcript specific manipulation at the complex Brain-derived neurotrophic factor (Bdnf) gene. Our findings advance this improved CRISPRi technology for use in neuronal systems for the first time, potentially enabling improved ability to manipulate gene expression states in the nervous system.

scholarly journals Acute condensin depletion causes genome decompaction without altering the level of global gene expression in Saccharomyces cerevisiae

2017 ◽  
Author(s):  
Matthew Robert Paul ◽  
Tovah Elise Markowitz ◽  
Andreas Hochwagen ◽  
Sevinç Ercan
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Genome Organization ◽  
Large Scale ◽  
Global Gene Expression ◽  
Higher Order ◽  
Gene Clustering ◽  
Global Changes ◽  
Chromatin Compaction ◽  
And Function

AbstractCondensins are broadly conserved chromosome organizers that function in chromatin compaction and transcriptional regulation, but to what extent these two functions are linked has remained unclear. Here, we analyzed the effect of condensin inactivation on genome compaction and global gene expression in the yeast Saccharomyces cerevisiae. Spike-in-controlled 3C-seq analysis revealed that acute condensin inactivation leads to a global decrease in close-range chromosomal interactions as well as more specific losses of homotypic tRNA gene clustering. In addition, a condensin-rich topologically associated domain between the ribosomal DNA and the centromere on chromosome XII is lost upon condensin inactivation. Unexpectedly, these large-scale changes in chromosome architecture are not associated with global changes in transcript levels as determined by spike-in-controlled mRNA-seq analysis. Our data suggest that the global transcriptional program of S. cerevisiae is resistant to condensin inactivation and the associated profound changes in genome organization.Significance StatementGene expression occurs in the context of higher-order chromatin organization, which helps compact the genome within the spatial constraints of the nucleus. To what extent higher-order chromatin compaction affects gene expression remains unknown. Here, we show that gene expression and genome compaction can be uncoupled in the single-celled model eukaryote Saccharomyces cerevisiae. Inactivation of the conserved condensin complex, which also organizes the human genome, leads to broad genome decompaction in this organism. Unexpectedly, this reorganization has no immediate effect on the transcriptome. These findings indicate that the global gene expression program is robust to large-scale changes in genome architecture in yeast, shedding important new light on the evolution and function of genome organization in gene regulation.

scholarly journals Retinal miRNA Functions in Health and Disease

Genes ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 377 ◽  
Author(s):  
Marta Zuzic ◽  
Jesus Eduardo Rojo Arias ◽  
Stefanie Gabriele Wohl ◽  
Volker Busskamp
Keyword(s):  
Gene Expression ◽  
Visual Impairment ◽  
Current Knowledge ◽  
Cell Types ◽  
Therapeutic Agents ◽  
Retinal Cell ◽  
Mrna Targets ◽  
Health And Disease ◽  
Cell Type Specific ◽  
And Function

The health and function of our visual system relies on accurate gene expression. While many genetic mutations are associated with visual impairment and blindness, we are just beginning to understand the complex interplay between gene regulation and retinal pathologies. MicroRNAs (miRNAs), a class of non-coding RNAs, are important regulators of gene expression that exert their function through post-transcriptional silencing of complementary mRNA targets. According to recent transcriptomic analyses, certain miRNA species are expressed in all retinal cell types, while others are cell type-specific. As miRNAs play important roles in homeostasis, cellular function, and survival of differentiated retinal cell types, their dysregulation is associated with retinal degenerative diseases. Thus, advancing our understanding of the genetic networks modulated by miRNAs is central to harnessing their potential as therapeutic agents to overcome visual impairment. In this review, we summarize the role of distinct miRNAs in specific retinal cell types, the current knowledge on their implication in inherited retinal disorders, and their potential as therapeutic agents.

scholarly journals Intra-individual methylomics detects the impact of early-life adversity

2018 ◽  
Author(s):  
Shan Jiang ◽  
Noriko Kamei ◽  
Jessica L. Bolton ◽  
Xinyi Ma ◽  
Hal S. Stern ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Fate ◽  
Early Life ◽  
Large Scale ◽  
Life Experience ◽  
Early Life Adversity ◽  
Health And Disease ◽  
Genetic And Environmental Factors ◽  
And Function ◽  
The Impact

AbstractGenetic and environmental factors interact during sensitive periods early in life to influence mental health and disease via epigenetic processes such as DNA methylation. However, it is not known if DNA methylation changes outside the brain provide an ‘epigenetic signature’ of early-life experiences. Here, we employed a novel intra-individual approach by testing DNA methylation from buccal cells of individual rats before and immediately after exposure to one week of typical or adverse life experience. We find that whereas inter-individual changes in DNA methylation reflect the effect of age, DNA methylation changes within paired DNA samples from the same individual reflect the impact of diverse neonatal experiences. Genes coding for critical cellular–metabolic enzymes, ion channels and receptors were more methylated in pups exposed to the adverse environment, predictive of their repression. In contrast, the adverse experience was associated with less methylation on genes involved in pathways of death and inflammation as well as cell-fate related transcription factors, indicating their potential upregulation. Thus, intra-individual methylome signatures indicate large-scale transcription-driven alterations of cellular fate, growth and function.

scholarly journals Intra-individual methylomics detects the impact of early-life adversity

2019 ◽  
Vol 2 (2) ◽  
pp. e201800204 ◽  
Author(s):  
Shan Jiang ◽  
Noriko Kamei ◽  
Jessica L Bolton ◽  
Xinyi Ma ◽  
Hal S Stern ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Fate ◽  
Early Life ◽  
Large Scale ◽  
Life Experience ◽  
Early Life Adversity ◽  
Health And Disease ◽  
Genetic And Environmental Factors ◽  
And Function ◽  
The Impact

Genetic and environmental factors interact during sensitive periods early in life to influence mental health and disease via epigenetic processes such as DNA methylation. However, it is not known if DNA methylation changes outside the brain provide an “epigenetic signature” of early-life experiences. Here, we used a novel intra-individual approach by testing DNA methylation from buccal cells of individual rats before and immediately after exposure to one week of typical or adverse life experience. We find that whereas inter-individual changes in DNA methylation reflect the effect of age, DNA methylation changes within paired DNA samples from the same individual reflect the impact of diverse neonatal experiences. Genes coding for critical cellular metabolic enzymes, ion channels, and receptors were more methylated in pups exposed to the adverse environment, predictive of their repression. In contrast, the adverse experience was associated with less methylation on genes involved in pathways of death and inflammation as well as cell-fate–related transcription factors, indicating their potential up-regulation. Thus, intra-individual methylome signatures indicate large-scale transcription-driven alterations of cellular fate, growth, and function.

The Laryngeal Epithelium in Reflux

2011 ◽  
Vol 21 (3) ◽  
pp. 112-117 ◽  
Author(s):  
Elizabeth Erickson-Levendoski ◽  
Mahalakshmi Sivasankar
Keyword(s):  
Laryngopharyngeal Reflux ◽  
Critical Role ◽  
Structure And Function ◽  
Laryngeal Disease ◽  
Health And Disease ◽  
And Function ◽  
The Impact

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.

Retinal gene expression shows compartment specific differences in health and disease

2014 ◽  
Vol 9 (S 01) ◽  
Author(s):  
C Weinold ◽  
M Kolibabka ◽  
G Molema ◽  
D Margerie ◽  
HP Hammes
Keyword(s):  
Gene Expression ◽  
Health And Disease

Plant hormones, plant growth regulators

2014 ◽  
Vol 155 (26) ◽  
pp. 1011-1018 ◽  
Author(s):  
György Végvári ◽  
Edina Vidéki
Keyword(s):  
Nervous System ◽  
Growth And Development ◽  
Large Scale ◽  
Essential Role ◽  
Higher Plants ◽  
Structure And Function ◽  
Wide Sense ◽  
Large Scale Integration ◽  
Scale Integration ◽  
And Function

Plants seem to be rather defenceless, they are unable to do motion, have no nervous system or immune system unlike animals. Besides this, plants do have hormones, though these substances are produced not in glands. In view of their complexity they lagged behind animals, however, plant organisms show large scale integration in their structure and function. In higher plants, such as in animals, the intercellular communication is fulfilled through chemical messengers. These specific compounds in plants are called phytohormones, or in a wide sense, bioregulators. Even a small quantity of these endogenous organic compounds are able to regulate the operation, growth and development of higher plants, and keep the connection between cells, tissues and synergy beween organs. Since they do not have nervous and immume systems, phytohormones play essential role in plants’ life. Orv. Hetil., 2014, 155(26), 1011–1018.

Sign in / Sign up

Export Citation Format

Share Document