scholarly journals Analysis of transcriptional changes associated with pubertal development

2021 ◽  
Author(s):  
Justyna Resztak ◽  
Jane Choe ◽  
Julong Wei ◽  
Rachel Bruinsma ◽  
Russell Houpt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Pubertal Development ◽  
Genetic Effect ◽  
Age At Menarche ◽  
Immune Gene ◽  
Study Approach ◽  
Transcriptional Changes ◽  
Immune Changes ◽  
Short Time

Puberty is an important developmental period marked by hormonal, metabolic and immune changes, which have been implicated in predisposition to immune diseases later in life. Yet, little is known about the gene expression changes in immune cells that occur during pubertal development. In a longitudinal cohort of 251 children we assessed pubertal development and leukocyte gene expression. We identified largely overlapping gene expression changes in boys and girls for thousands of genes over a short time period. For 108 genes we detected gene expression changes associated with pubertal development. Substantial transcriptional changes were detected between pre- and post-menarcheal girls, which suggested a shift from predominantly innate to adaptive immunity as girls sexually matured. We identified genetic effects on gene expression that dynamically change during pubertal development for IGKV1-27 and PGAP1 in males, DSC1 and TRBV30 in females. We discovered that menarche is associated with a change in sign of a genetic effect on the expression of the asthma-associated gene FLOT2. Using a Transcriptome-Wide Association Study approach, we discovered that in girls, gene expression changes during puberty are associated with age at menarche. For example, expression of the endometrial cancer risk gene EEFSEC increases as girls become older, suggesting a link between age at menarche, transcriptional changes happening during puberty and poor health outcomes. These findings shed light on immune gene expression processes accompanying puberty and can advance the understanding of the molecular mechanisms through which pubertal development relates to immune diseases later in life.

scholarly journals Transcriptional signatures throughout development: the effects of mouse embryo manipulation in vitro

Reproduction ◽  
2017 ◽  
Vol 153 (1) ◽  
pp. 107-122 ◽  
Author(s):  
Sky K Feuer ◽  
Xiaowei Liu ◽  
Annemarie Donjacour ◽  
Rhodel Simbulan ◽  
Emin Maltepe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Preimplantation Embryo ◽  
Environmental Exposures ◽  
Developmental Time ◽  
Transcriptional Responses ◽  
Transcriptional Changes ◽  
Specific Impact

Stressful environmental exposures incurred early in development can affect postnatal metabolic health and susceptibility to non-communicable diseases in adulthood, although the molecular mechanisms by which this occurs have yet to be elucidated. Here, we use a mouse model to investigate how assortedin vitroexposures restricted exclusively to the preimplantation period affect transcription both acutely in embryos and long term in subsequent offspring adult tissues, to determine if reliable transcriptional markers ofin vitrostress are present at specific developmental time points and throughout development. Eachin vitrofertilization or embryo culture environment led to a specific and unique blastocyst transcriptional profile, but we identified a common 18-gene and 9-pathway signature of preimplantation embryo manipulation that was present in allin vitroembryos irrespective of culture condition or method of fertilization. This fingerprint did not persist throughout development, and there was no clear transcriptional cohesion between adult IVF offspring tissues or compared to their preceding embryos, indicating a tissue-specific impact ofin vitrostress on gene expression. However, the transcriptional changes present in each IVF tissue were targeted by the same upstream transcriptional regulators, which provide insight as to how acute transcriptional responses to stressful environmental exposures might be preserved throughout development to influence adult gene expression.

scholarly journals The interdependence of gene-regulatory elements and the 3D genome

2018 ◽  
Vol 218 (1) ◽  
pp. 12-26 ◽  
Author(s):  
Marit W. Vermunt ◽  
Di Zhang ◽  
Gerd A. Blobel
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Regulatory Elements ◽  
3D Genome ◽  
Gene Positioning ◽  
Transcriptional Changes ◽  
Gene Regulatory Elements ◽  
Chromatin Folding ◽  
Gene Regulatory ◽  
Relationship Of

Imaging studies, high-resolution chromatin conformation maps, and genome-wide occupancy data of architectural proteins have revealed that genome topology is tightly intertwined with gene expression. Cross-talk between gene-regulatory elements is often organized within insulated neighborhoods, and regulatory cues that induce transcriptional changes can reshape chromatin folding patterns and gene positioning within the nucleus. The cause–consequence relationship of genome architecture and gene expression is intricate, and its molecular mechanisms are under intense investigation. Here, we review the interdependency of transcription and genome organization with emphasis on enhancer–promoter contacts in gene regulation.

scholarly journals Transcriptomics identifies STAT3 as a key regulator of hippocampal gene expression and anhedonia during withdrawal from chronic alcohol exposure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wei-Yang Chen ◽  
Hu Chen ◽  
Kana Hamada ◽  
Eleonora Gatta ◽  
Ying Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alcohol Drinking ◽  
Alcohol Withdrawal ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Alcohol Exposure ◽  
Immune Gene ◽  
Chronic Alcohol ◽  
Chronic Alcohol Exposure

AbstractAlcohol use disorder (AUD) is highly comorbid with depression. Withdrawal from chronic alcohol drinking results in depression and understanding brain molecular mechanisms that drive withdrawal-related depression is important for finding new drug targets to treat these comorbid conditions. Here, we performed RNA sequencing of the rat hippocampus during withdrawal from chronic alcohol drinking to discover key signaling pathways involved in alcohol withdrawal-related depressive-like behavior. Data were analyzed by weighted gene co-expression network analysis to identify several modules of co-expressed genes that could have a common underlying regulatory mechanism. One of the hub, or highly interconnected, genes in module 1 that increased during alcohol withdrawal was the transcription factor, signal transducer and activator of transcription 3 (Stat3), a known regulator of immune gene expression. Total and phosphorylated (p)STAT3 protein levels were also increased in the hippocampus during withdrawal after chronic alcohol exposure. Further, pSTAT3 binding was enriched at the module 1 genes Gfap, Tnfrsf1a, and Socs3 during alcohol withdrawal. Notably, pSTAT3 and its target genes were elevated in the postmortem hippocampus of human subjects with AUD when compared with control subjects. To determine the behavioral relevance of STAT3 activation during alcohol withdrawal, we treated rats with the STAT3 inhibitor stattic and tested for sucrose preference as a measure of anhedonia. STAT3 inhibition alleviated alcohol withdrawal-induced anhedonia. These results demonstrate activation of STAT3 signaling in the hippocampus during alcohol withdrawal in rats and in human AUD subjects, and suggest that STAT3 could be a therapeutic target for reducing comorbid AUD and depression.

scholarly journals P854 Construction of the immune landscape of durable response to checkpoint blockade therapy by integrating publicly available datasets

2020 ◽  
Vol 8 (Suppl 1) ◽  
pp. A5.2-A6
Author(s):  
Nils-Petter Rudqvist ◽  
Roberta Zappasodi ◽  
Daniel Wells ◽  
Vésteinn Thorsson ◽  
Alexandria Cogdill ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Checkpoint ◽  
Molecular Mechanisms ◽  
Cross Validation ◽  
Immune Cell ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Immune Gene ◽  
List Type ◽  
Durable Response

BackgroundImmune checkpoint blockade (ICB) has revolutionized cancer treatment. However, long-term benefits are only achieved in a small fraction of patients. Understanding the mechanisms underlying ICB activity is key to improving the efficacy of immunotherapy. A major limitation to uncovering these mechanisms is the limited number of responders within each ICB trial. Integrating data from multiple studies of ICB would help overcome this issue and more reliably define the immune landscape of durable responses. Towards this goal, we formed the TimIOs consortium, comprising researchers from the Society for Immunotherapy of Cancer Sparkathon TimIOs Initiative, the Parker Institute of Cancer Immunotherapy, the University of North Carolina-Chapel Hill, and the Institute for Systems Biology. Together, we aim to improve the understanding of the molecular mechanisms associated with defined outcomes to ICB, by building on our joint and multifaceted expertise in the field of immuno-oncology. To determine the feasibility and relevance of our approach, we have assembled a compendium of publicly available gene expression datasets from clinical trials of ICB. We plan to analyze this data using a previously reported pipeline that successfully determined main cancer immune-subtypes associated with survival across multiple cancer types in TCGA.1MethodsRNA sequencing data from 1092 patients were uniformly reprocessed harmonized, and annotated with predefined clinical parameters. We defined a comprehensive set of immunogenomics features, including immune gene expression signatures associated with treatment outcome,1,2 estimates of immune cell proportions, metabolic profiles, and T and B cell receptor repertoire, and scored all compendium samples for these features. Elastic net regression models with parameter optimization done via Monte Carlo cross-validation and leave-one-out cross-validation were used to analyze the capacity of an integrated immunogenomics model to predict durable clinical benefit following ICB treatment.ResultsOur preliminary analyses confirmed an association between the expression of an IFN-gamma signature in tumor (1) and better outcomes of ICB, highlighting the feasibility of our approach.ConclusionsIn line with analysis of pan-cancer TCGA datasets using this strategy (1), we expect to identify analogous immune subtypes characterizing baseline tumors from patients responding to ICB. Furthermore, we expect to find that these immune subtypes will have different importance in the model predicting response and survival. Results of this study will be incorporated into the Cancer Research Institute iAtlas Portal, to facilitate interactive exploration and hypothesis testing.ReferencesThorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Yang T-H O, Porta-Pardo E. Gao GF, Plaisier CL, Eddy JA, et al. The Immune Landscape of Cancer. Immunity 2018; 48(4): 812–830.e14. https://doi.org/10.1016/j.immuni.2018.03.023.Auslander N, Zhang G, Lee JS, Frederick DT, Miao B, Moll T, Tian T, Wei Z, Madan S, Sullivan RJ, et al. Robust Prediction of Response to Immune Checkpoint Blockade Therapy in Metastatic Melanoma. Nat. Med 2018; 24(10): 1545. https://doi.org/10.1038/s41591-018-0157-9.

scholarly journals Age-related changes of gene expression in the neocortex: Preliminary data on RNA-Seq of the transcriptome in three functionally distinct cortical areas

2012 ◽  
Vol 24 (4) ◽  
pp. 1427-1442 ◽  
Author(s):  
Oksana Yu. Naumova ◽  
Dean Palejev ◽  
Natalia V. Vlasova ◽  
Maria Lee ◽  
Sergei Yu. Rychkov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Rna Seq ◽  
Signaling Systems ◽  
Cortical Areas ◽  
Age Related ◽  
Transcriptional Changes ◽  
Atypical Development ◽  
The Brain ◽  
Age Related Changes

AbstractThe study of gene expression (i.e., the study of the transcriptome) in different cells and tissues allows us to understand the molecular mechanisms of their differentiation, development and functioning. In this article, we describe some studies of gene-expression profiling for the purposes of understanding developmental (age-related) changes in the brain using different technologies (e.g., DNA-Microarray) and the new and increasingly popular RNA-Seq. We focus on advancements in studies of gene expression in the human brain, which have provided data on the structure and age-related variability of the transcriptome in the brain. We present data on RNA-Seq of the transcriptome in three distinct areas of the neocortex from different ages: mature and elderly individuals. We report that most age-related transcriptional changes affect cellular signaling systems, and, as a result, the transmission of nerve impulses. In general, the results demonstrate the high potential of RNA-Seq for the study of distinctive features of gene expression among cortical areas and the changes in expression through normal and atypical development of the central nervous system.

scholarly journals RNA-Seq analysis of differential gene expression in Betula luminifera xylem during the early stages of tension wood formation

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5427 ◽  
Author(s):  
Miaomiao Cai ◽  
Huahong Huang ◽  
Fei Ni ◽  
Zaikang Tong ◽  
Erpei Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tension Wood ◽  
Molecular Mechanisms ◽  
Southern China ◽  
Lignin Biosynthesis ◽  
Wood Formation ◽  
Cellulose Synthesis ◽  
Early Stages ◽  
Transcriptional Changes ◽  
Betula Luminifera

Background Betula luminifera H. Winkler, which is widely distributed in southern China, is an economically important broadleaf tree species. However, little genomic information of B. luminifera is available, and little is known about the molecular mechanisms of wood formation in this species. Meanwhile, few efforts have focused on investigating the early transcriptional changes during tension wood formation in woody plants. Results A reference transcriptome dataset was first generated containing 45,700 Unigenes, and 35,135 (76.9%) Unigenes were annotated by a BLAST similarity search against four public databases. Then, based on an anatomical investigation, the global gene expression changes during the early stages of tension wood formation were analyzed. Gene expression profiling showed that a total of 13,273 Unigenes were differentially regulated during the early stages of tension wood formation. Most genes involved in cellulose and lignin biosynthesis were highlighted to reveal their biological importance in tension wood formation. In addition, the transcription levels of many genes involved in the auxin response pathway were significantly changed during the early stages of tension wood formation. Furthermore, 18 TFs co-expressed with key enzymes of cellulose synthesis were identified. Conclusions Our results revealed the transcriptional changes associated with TW formation and identified potential key genes in the regulation of this process. These results will help to dissect the molecular mechanism of wood formation and provide key candidate genes for marker-assisted selection in B. luminifera.

scholarly journals Transcriptional changes and preservation of bone mass in hibernating black bears

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna V. Goropashnaya ◽  
Øivind Tøien ◽  
Thiruvarangan Ramaraj ◽  
Anitha Sundararajan ◽  
Faye D. Schilkey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Mass ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Tricarboxylic Acid Cycle ◽  
Mammalian Species ◽  
Osteoclast Differentiation ◽  
Gene Set Enrichment Analysis ◽  
Gene Sets ◽  
Transcriptional Changes

AbstractPhysical inactivity leads to losses of bone mass and strength in most mammalian species. In contrast, hibernating bears show no bone loss over the prolonged periods (4–6 months) of immobility during winter, which suggests that they have adaptive mechanisms to preserve bone mass. To identify transcriptional changes that underlie molecular mechanisms preventing disuse osteoporosis, we conducted a large-scale gene expression screening in the trabecular bone and bone marrow, comparing hibernating and summer active bears through sequencing of the transcriptome. Gene set enrichment analysis showed a coordinated down-regulation of genes involved in bone resorption, osteoclast differentiation and signaling, and apoptosis during hibernation. These findings are consistent with previous histological findings and likely contribute to the preservation of bone during the immobility of hibernation. In contrast, no significant enrichment indicating directional changes in gene expression was detected in the gene sets of bone formation and osteoblast signaling in hibernating bears. Additionally, we revealed significant and coordinated transcriptional induction of gene sets involved in aerobic energy production including fatty acid beta oxidation, tricarboxylic acid cycle, oxidative phosphorylation, and mitochondrial metabolism. Mitochondrial oxidation was likely up-regulated by transcriptionally induced AMPK/PGC1α pathway, an upstream stimulator of mitochondrial function.

scholarly journals Y-linked variation for autosomal immune gene regulation has the potential to shape sexually dimorphic immunity

2015 ◽  
Vol 282 (1820) ◽  
pp. 20151301 ◽  
Author(s):  
Ian C. Kutch ◽  
Kenneth M. Fedorka
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Y Chromosome ◽  
Molecular Mechanisms ◽  
Wild Population ◽  
Immune Gene ◽  
Sexually Dimorphic ◽  
Male Fitness ◽  
Male And Female ◽  
Y Chromosomes

Sexually dimorphic phenotypes arise from the differential expression of male and female shared genes throughout the genome. Unfortunately, the underlying molecular mechanisms by which dimorphic regulation manifests and evolves are unclear. Recent work suggests that Y-chromosomes may play an important role, given that Drosophila melanogaster Ys were shown to influence the regulation of hundreds of X and autosomal genes. For Y-linked regulatory variation (YRV) to facilitate sexually dimorphic evolution, however, it must exist within populations (where selection operates) and influence male fitness. These criteria have seldom been investigated, leaving the potential for dimorphic evolution via YRV unclear. Interestingly, male and female D. melanogaster differ in immune gene regulation. Furthermore, immune gene regulation appears to be influenced by the Y-chromosome, suggesting it may contribute to dimorphic immune evolution. We address this possibility by introgressing Y-chromosomes from a single wild population into an isogenic background (to create Y-lines) and assessing immune gene regulation and bacterial defence. We found that Y-line males differed in their immune gene regulation and their ability to defend against Serratia marcescens. Moreover, gene expression and bacterial defence were positively genetically correlated. These data indicate that the Y-chromosome has the potential to shape the evolution of sexually dimorphic immunity in this system.

scholarly journals Genomic architecture and sexually dimorphic expression underlying immunity in the red mason bee, Osmia bicornis

2021 ◽  
Author(s):  
Jannik Sven Moellmann ◽  
Thomas Joseph Colgan
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Solitary Bees ◽  
Immune Gene ◽  
Gene Repertoire ◽  
Important Species ◽  
Osmia Bicornis ◽  
Immune Genes ◽  
Immune Gene Expression ◽  
Genomic Architecture

Insect pollinators provide crucial ecosystem services yet face increasing environmental pressures. The challenges posed by novel and reemerging pathogens on bee health means we need to improve our understanding of the immune system, an important barrier to infections and disease. Despite its importance, for certain ecologically important species, such as solitary bees, our understanding of the genomic basis and molecular mechanisms underlying immune potential, and how intrinsic and extrinsic factors may influence immune gene expression is lacking. Here, to improve our understanding of the genomic architecture underlying immunity of a key solitary bee pollinator, we characterised putative immune genes of the red mason bee, Osmia bicornis. In addition, we used publicly available RNA-seq datasets to determine how sexes differ in immune gene expression and splicing but also how pesticide exposure may affect immune gene expression in females. Through comparative genomics, we reveal an evolutionary conserved set of more than 500 putative immune-related genes. We found genome-wide patterns of sex-biased gene expression, including immune genes involved in antiviral-defence. Interestingly, the expression of certain immune genes were also affected by exposure to common neonicotinoids, particularly genes related to haemocyte proliferation. Collectively, our study provides important insights into the gene repertoire, regulation and expression differences in the sexes of O. bicornis, as well as providing additional support for how neonicotinoids can affect immune gene expression, which may affect the capacity of solitary bees to respond to pathogenic threats.

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