Spatial and temporal diversity of glycome expression in mammalian brain

Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale “omics” studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties. Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development. We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse. Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse. We found that glycan expression profiles were dynamically regulated during postnatal developments. A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain were also identified. Interestingly, changes primarily attributed to sialylated and fucosylated glycans were extensively observed during PFC development. Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development. Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.

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Discovering Distinct Patterns in Gene Expression Profiles

Journal of Integrative Bioinformatics ◽

10.1515/jib-2008-105 ◽

2008 ◽

Vol 5 (2) ◽

Cited By ~ 1

Author(s):

Li Teng ◽

Laiwan Chan

Keyword(s):

Gene Expression ◽

Large Scale ◽

Expression Profiles ◽

Expression Patterns ◽

Gene Expression Profiles ◽

Clustering Methods ◽

Gene Expressions ◽

Real Gene ◽

Large Scale Dataset ◽

Coexpressed Genes

SummaryTraditional analysis of gene expression profiles use clustering to find groups of coexpressed genes which have similar expression patterns. However clustering is time consuming and could be diffcult for very large scale dataset. We proposed the idea of Discovering Distinct Patterns (DDP) in gene expression profiles. Since patterns showing by the gene expressions reveal their regulate mechanisms. It is significant to find all different patterns existing in the dataset when there is little prior knowledge. It is also a helpful start before taking on further analysis. We propose an algorithm for DDP by iteratively picking out pairs of gene expression patterns which have the largest dissimilarities. This method can also be used as preprocessing to initialize centers for clustering methods, like K-means. Experiments on both synthetic dataset and real gene expression datasets show our method is very effective in finding distinct patterns which have gene functional significance and is also effcient.

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Comparison of gene expression in fresh and frozen–thawed human preimplantation embryos

Reproduction ◽

10.1530/rep-12-0047 ◽

2012 ◽

Vol 144 (5) ◽

pp. 569-582 ◽

Cited By ~ 31

Author(s):

Lisa Shaw ◽

Sharon F Sneddon ◽

Daniel R Brison ◽

Susan J Kimber

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Expression Patterns ◽

Developmental Expression ◽

Preimplantation Embryos ◽

Human Embryos ◽

Molecular Events ◽

Reliable Source ◽

Human Preimplantation Embryos ◽

Early Human

Identification and characterisation of differentially regulated genes in preimplantation human embryonic development are required to improve embryo quality and pregnancy rates in IVF. In this study, we examined expression of a number of genes known to be critical for early development and compared expression profiles in individual preimplantation human embryos to establish any differences in gene expression in fresh compared to frozen–thawed embryos used routinely in IVF. We analysed expression of 19 genes by cDNA amplification followed by quantitative real-time PCR in a panel of 44 fresh and frozen–thawed human preimplantation embryos. Fresh embryos were obtained from surplus early cleavage stage embryos and frozen–thawed embryos from cryopreserved 2PN embryos. Our aim was to determine differences in gene expression between fresh and frozen–thawed human embryos, but we also identified differences in developmental expression patterns for particular genes. We show that overall gene expression among embryos of the same stage is highly variable and our results indicate that expression levels between groups did differ and differences in expression of individual genes was detected. Our results show that gene expression from frozen–thawed embryos is more consistent when compared with fresh, suggesting that cryopreserved embryos may represent a reliable source for studying the molecular events underpinning early human embryo development.

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CFTR ΔF508 mutation has minimal effect on the gene expression profile of differentiated human airway epithelia

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00065.2005 ◽

2005 ◽

Vol 289 (4) ◽

pp. L545-L553 ◽

Cited By ~ 29

Author(s):

Joseph Zabner ◽

Todd E. Scheetz ◽

Hakeem G. Almabrazi ◽

Thomas L. Casavant ◽

Jian Huang ◽

...

Keyword(s):

Gene Expression ◽

Cystic Fibrosis ◽

Large Scale ◽

Expression Profiles ◽

Expression Patterns ◽

Primary Cultures ◽

Gene Expression Profiles ◽

Filter Method ◽

Tissue Destruction ◽

Airway Epithelia

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial chloride channel regulated by phosphorylation. Most of the disease-associated morbidity is the consequence of chronic lung infection with progressive tissue destruction. As an approach to investigate the cellular effects of CFTR mutations, we used large-scale microarray hybridization to contrast the gene expression profiles of well-differentiated primary cultures of human CF and non-CF airway epithelia grown under resting culture conditions. We surveyed the expression profiles for 10 non-CF and 10 ΔF508 homozygote samples. Of the 22,283 genes represented on the Affymetrix U133A GeneChip, we found evidence of significant changes in expression in 24 genes by two-sample t-test ( P < 0.00001). A second, three-filter method of comparative analysis found no significant differences between the groups. The levels of CFTR mRNA were comparable in both groups. There were no significant differences in the gene expression patterns between male and female CF specimens. There were 18 genes with significant increases and 6 genes with decreases in CF relative to non-CF samples. Although the function of many of the differentially expressed genes is unknown, one transcript that was elevated in CF, the KCl cotransporter (KCC4), is a candidate for further study. Overall, the results indicate that CFTR dysfunction has little direct impact on airway epithelial gene expression in samples grown under these conditions.

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Dynamical consequences of regional heterogeneity in the brain’s transcriptional landscape

10.1101/2020.10.28.359943 ◽

2020 ◽

Cited By ~ 1

Author(s):

Gustavo Deco ◽

Kevin Aquino ◽

Aurina Arnatkevičiūtė ◽

Stuart Oldham ◽

Kristina Sabaroedin ◽

...

Keyword(s):

Gene Expression ◽

Large Scale ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Global Gene Expression ◽

Brain Regions ◽

Biophysical Model ◽

Neuronal Dynamics ◽

Regional Heterogeneity ◽

Magnetic Resonance Imaging Mri

AbstractBrain regions vary in their molecular and cellular composition, but how this heterogeneity shapes neuronal dynamics is unclear. Here, we investigate the dynamical consequences of regional heterogeneity using a biophysical model of whole-brain functional magnetic resonance imaging (MRI) dynamics in humans. We show that models in which transcriptional variations in excitatory and inhibitory receptor (E:I) gene expression constrain regional heterogeneity more accurately reproduce the spatiotemporal structure of empirical functional connectivity estimates than do models constrained by global gene expression profiles and MRI-derived estimates of myeloarchitecture. We further show that regional heterogeneity is essential for yielding both ignition-like dynamics, which are thought to support conscious processing, and a wide variance of regional activity timescales, which supports a broad dynamical range. We thus identify a key role for E:I heterogeneity in generating complex neuronal dynamics and demonstrate the viability of using transcriptional data to constrain models of large-scale brain function.

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Transcriptome Profiling of Adipose Tissue Reveals Depot-Specific Metabolic Alterations Among Patients with Colorectal Cancer

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2019-00461 ◽

2019 ◽

Vol 104 (11) ◽

pp. 5225-5237 ◽

Cited By ~ 3

Author(s):

Mariam Haffa ◽

Andreana N Holowatyj ◽

Mario Kratz ◽

Reka Toth ◽

Axel Benner ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Adipose Tissue ◽

Large Scale ◽

Expression Profiles ◽

Expression Patterns ◽

Human Study ◽

Subcutaneous Fat ◽

Specific Gene ◽

Adipose Tissue Depots

Abstract Context Adipose tissue inflammation and dysregulated energy homeostasis are key mechanisms linking obesity and cancer. Distinct adipose tissue depots strongly differ in their metabolic profiles; however, comprehensive studies of depot-specific perturbations among patients with cancer are lacking. Objective We compared transcriptome profiles of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from patients with colorectal cancer and assessed the associations of different anthropometric measures with depot-specific gene expression. Design Whole transcriptomes of VAT and SAT were measured in 233 patients from the ColoCare Study, and visceral and subcutaneous fat area were quantified via CT. Results VAT compared with SAT showed elevated gene expression of cytokines, cell adhesion molecules, and key regulators of metabolic homeostasis. Increased fat area was associated with downregulated lipid and small molecule metabolism and upregulated inflammatory pathways in both compartments. Comparing these patterns between depots proved specific and more pronounced gene expression alterations in SAT and identified unique associations of integrins and lipid metabolism–related enzymes. VAT gene expression patterns that were associated with visceral fat area poorly overlapped with patterns associated with self-reported body mass index (BMI). However, subcutaneous fat area and BMI showed similar associations with SAT gene expression. Conclusions This large-scale human study demonstrates pronounced disparities between distinct adipose tissue depots and reveals that BMI poorly correlates with fat mass–associated changes in VAT. Taken together, these results provide crucial evidence for the necessity to differentiate between distinct adipose tissue depots for a correct characterization of gene expression profiles that may affect metabolic health of patients with colorectal cancer.

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Maternal Dietary Docosahexaenoic Acid Alters Lipid Peroxidation Products and (n-3)/(n-6) Fatty Acid Balance in Offspring Mice

Metabolites ◽

10.3390/metabo9030040 ◽

2019 ◽

Vol 9 (3) ◽

pp. 40 ◽

Cited By ~ 9

Author(s):

Bo Yang ◽

Runting Li ◽

Taeseon Woo ◽

Jimmy Browning ◽

Hailong Song ◽

...

Keyword(s):

Lipid Peroxidation ◽

Docosahexaenoic Acid ◽

Maternal Diet ◽

Brain Regions ◽

Diet Group ◽

Mammalian Brain ◽

Enzymatic Reactions ◽

Functional Changes ◽

Lipid Peroxidation Products ◽

Brain Functions

The abundance of docosahexaenoic acid (DHA) in the mammalian brain has generated substantial interest in the search for its roles in regulating brain functions. Our recent study with a gene/stress mouse model provided evidence to support the ability for the maternal supplement of DHA to alleviate autism-associated behavior in the offspring. DHA and arachidonic acid (ARA) are substrates of enzymatic and non-enzymatic reactions, and lipid peroxidation results in the production of 4-hydroxyhexenal (4-HHE) and 4-hydroxynonenal (4-HNE), respectively. In this study, we examine whether a maternal DHA-supplemented diet alters fatty acids (FAs), as well as lipid peroxidation products in the pup brain, heart and plasma by a targeted metabolite approach. Pups in the maternal DHA-supplemented diet group showed an increase in DHA and a concomitant decrease in ARA in all brain regions examined. However, significant increases in 4-HHE, and not 4-HNE, were found mainly in the cerebral cortex and hippocampus. Analysis of heart and plasma showed large increases in DHA and 4-HHE, but a significant decrease in 4-HNE levels only in plasma. Taken together, the DHA-supplemented maternal diet alters the (n-3)/(n-6) FA ratio, and increases 4-HHE levels in pup brain, heart and plasma. These effects may contribute to the beneficial effects of DHA on neurodevelopment, as well as functional changes in other body organs.

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Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1411263112 ◽

2015 ◽

Vol 112 (22) ◽

pp. 6855-6862 ◽

Cited By ~ 91

Author(s):

Loyal A. Goff ◽

Abigail F. Groff ◽

Martin Sauvageau ◽

Zachary Trayes-Gibson ◽

Diana B. Sanchez-Gomez ◽

...

Keyword(s):

Neural Development ◽

Expression Patterns ◽

Noncoding Rnas ◽

Brain Regions ◽

Long Noncoding Rnas ◽

Adult Brain ◽

Mammalian Brain ◽

Endogenous Expression ◽

Spatiotemporal Expression

Long noncoding RNAs (lncRNAs) have been implicated in numerous cellular processes including brain development. However, the in vivo expression dynamics and molecular pathways regulated by these loci are not well understood. Here, we leveraged a cohort of 13 lncRNA-null mutant mouse models to investigate the spatiotemporal expression of lncRNAs in the developing and adult brain and the transcriptome alterations resulting from the loss of these lncRNA loci. We show that several lncRNAs are differentially expressed both in time and space, with some presenting highly restricted expression in only selected brain regions. We further demonstrate altered regulation of genes for a large variety of cellular pathways and processes upon deletion of the lncRNA loci. Finally, we found that 4 of the 13 lncRNAs significantly affect the expression of several neighboring protein-coding genes in a cis-like manner. By providing insight into the endogenous expression patterns and the transcriptional perturbations caused by deletion of the lncRNA locus in the developing and postnatal mammalian brain, these data provide a resource to facilitate future examination of the specific functional relevance of these genes in neural development, brain function, and disease.

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Distinct properties in ventral pallidum projection neuron subtypes

10.1101/2021.11.15.468637 ◽

2021 ◽

Author(s):

Nimrod Bernat ◽

Rianne Campbell ◽

Hyungwoo Nam ◽

Mahashweta Basu ◽

Tal Odesser ◽

...

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Expression Patterns ◽

Critical Role ◽

Gene Expression Profiles ◽

Cell Types ◽

Projection Neuron ◽

Brain Regions ◽

Ventral Pallidum ◽

Lateral Habenula

The ventral pallidum (VP), a major component of the basal ganglia, plays a critical role in motivational disorders. It sends projections to many different brain regions but it is not yet known whether and how these projections differ in their cellular properties, gene expression patterns, connectivity and role in reward seeking. In this study, we focus on four major outputs of the VP - to the lateral hypothalamus (LH), ventral tegmental area (VTA), mediodorsal thalamus (MDT), and lateral habenula (LHb) - and examine the differences between them in 1) baseline gene expression profiles using projection-specific RNA-sequencing; 2) physiological parameters using whole-cell patch clamp; and 3) their influence on cocaine reward using chemogenetic tools. We show that these four VP efferents differ in all three aspects and highlight specifically differences between the projections to the LH and the VTA. These two projections originate largely from separate populations of neurons, express distinct sets of genes related to neurobiological functions, and show opposite physiological and behavioral properties. Collectively, our data demonstrates for the first time that VP neurons exhibit distinct molecular and cellular profiles in a projection-specific manner, suggesting that they represent different cell types.

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Scopolamine-induced Delirium Promotes Neuroinflammation and Neuropsychiatric Disorder in Mice

10.21203/rs.3.rs-126768/v1 ◽

2020 ◽

Author(s):

So Yeong Cheon ◽

Bon-Nyeo Koo ◽

So Yeon Kim ◽

Eun Hee Kam ◽

Junhyun Nam ◽

...

Keyword(s):

Gene Expression ◽

Inflammatory Cytokines ◽

Expression Profiles ◽

Expression Patterns ◽

Gene Expression Profiles ◽

Brain Regions ◽

Mice Model ◽

Tnf Α ◽

Compare Gene Expression ◽

Pro Inflammatory Cytokines

Abstract BackgroundPostoperative delirium is a common neuropsychiatric syndrome resulting in a high postsurgical mortality rate and decline in postdischarge function. Extensive research has been performed on both human and animal delirium models due to their clinical significance, focusing on systemic inflammation and consequent neuroinflammation playing a key in the pathogenesis of postoperative cognitive dysfunctions. Since animal models are widely utilized for pathophysiological study of neuropsychiatric disorders, this study aimed at examining the validity of the scopolamine-induced delirium mice model with respect to the neuroinflammatory hypothesis of delirium. MethodsMale C57BL/6 mice were treated with intraperitoneal scopolamine (2 mg/kg). Neurobehavioural tests were performed to evaluate the changes in cognitive functions, including learning and memory, and the level of anxiety after surgery or scopolamine treatment. The levels of pro-inflammatory cytokines (IL-1ꞵ, IL-18, and TNF-α) and inflammasome components (NLRP3, ASC, and caspase-1) in different brain regions were measured. Gene expression profiles were also examined using whole-genome RNA sequencing analyses to compare gene expression patterns of different mice models.Results Scopolamine treatment showed significant increase in the level of anxiety and impairments in memory and cognitive function associated with increased level of pro-inflammatory cytokines and NLRP3 inflammasome components. Genetic analysis confirmed the different expression patterns of the genes involved in immune response and inflammation and those related with the development of the nervous system in both surgery and scopolamine-induced mice models. Conclusions The scopolamine-induced delirium mice model successfully showed that analogous neuropsychiatric changes coincide with the neuroinflammatory hypothesis for pathogenesis of delirium.

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Moderate alcohol consumption alters both leucocyte gene expression profiles and circulating proteins related to immune response and lipid metabolism in men

British Journal Of Nutrition ◽

10.1017/s0007114511005988 ◽

2011 ◽

Vol 108 (4) ◽

pp. 620-627 ◽

Cited By ~ 18

Author(s):

Michel M. Joosten ◽

Marjan J. van Erk ◽

Linette Pellis ◽

Renger F. Witkamp ◽

Henk F. J. Hendriks

Keyword(s):

Gene Expression ◽

Immune Response ◽

Lipid Metabolism ◽

Alcohol Consumption ◽

Orange Juice ◽

Large Scale ◽

Disease Risk ◽

Expression Profiles ◽

Expression Patterns ◽

Moderate Alcohol Consumption

Moderate alcohol consumption has various effects on immune and inflammatory processes, which could accumulatively modulate chronic disease risk. So far, no comprehensive, integrative profiling has been performed to investigate the effects of longer-term alcohol consumption. Therefore, we studied the effects of alcohol consumption on gene expression patterns using large-scale profiling of whole-genome transcriptomics in blood cells and on a number of proteins in blood. In a randomised, open-label, cross-over trial, twenty-four young, normal-weight men consumed 100 ml vodka (30 g alcohol) with 200 ml orange juice or only orange juice daily during dinner for 4 weeks. After each period, blood was sampled for measuring gene expression and selected proteins. Pathway analysis of 345 down-regulated and 455 up-regulated genes revealed effects of alcohol consumption on various signalling responses, immune processes and lipid metabolism. Among the signalling processes, the most prominently changed was glucocorticoid receptor signalling. A network on immune response showed a down-regulated NF-κB gene expression together with increased plasma adiponectin and decreased pro-inflammatory IL-1 receptor antagonist and IL-18, and acute-phase proteins ferritin and α1-antitrypsin concentrations (all P < 0·05) after alcohol consumption. Furthermore, a network of gene expression changes related to lipid metabolism was observed, with a central role for PPARα which was supported by increased HDL-cholesterol and several apo concentrations (all P < 0·05) after alcohol consumption. In conclusion, an integrated approach of profiling both genes and proteins in blood showed that 4 weeks of moderate alcohol consumption altered immune responses and lipid metabolism.

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