Comprehensive epigenome characterization reveals diverse transcriptional regulation across human vascular endothelial cells

Abstract Background Endothelial cells (ECs) make up the innermost layer throughout the entire vasculature. Their phenotypes and physiological functions are initially regulated by developmental signals and extracellular stimuli. The underlying molecular mechanisms responsible for the diverse phenotypes of ECs from different organs are not well understood. Results To characterize the transcriptomic and epigenomic landscape in the vascular system, we cataloged gene expression and active histone marks in nine types of human ECs (generating 148 genome-wide datasets) and carried out a comprehensive analysis with chromatin interaction data. We developed a robust procedure for comparative epigenome analysis that circumvents variations at the level of the individual and technical noise derived from sample preparation under various conditions. Through this approach, we identified 3765 EC-specific enhancers, some of which were associated with disease-associated genetic variations. We also identified various candidate marker genes for each EC type. We found that the nine EC types can be divided into two subgroups, corresponding to those with upper-body origins and lower-body origins, based on their epigenomic landscape. Epigenomic variations were highly correlated with gene expression patterns, but also provided unique information. Most of the deferentially expressed genes and enhancers were cooperatively enriched in more than one EC type, suggesting that the distinct combinations of multiple genes play key roles in the diverse phenotypes across EC types. Notably, many homeobox genes were differentially expressed across EC types, and their expression was correlated with the relative position of each organ in the body. This reflects the developmental origins of ECs and their roles in angiogenesis, vasculogenesis and wound healing. Conclusions This comprehensive analysis of epigenome characterization of EC types reveals diverse transcriptional regulation across human vascular systems. These datasets provide a valuable resource for understanding the vascular system and associated diseases.

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Comprehensive epigenome characterization reveals diverse transcriptional regulation across human vascular endothelial cells

10.1101/756056 ◽

2019 ◽

Author(s):

Ryuichiro Nakato ◽

Youichiro Wada ◽

Ryo Nakaki ◽

Genta Nagae ◽

Yuki Katou ◽

...

Keyword(s):

Endothelial Cells ◽

Molecular Mechanisms ◽

Hox Genes ◽

Vascular System ◽

Vascular Endothelial Cells ◽

Chromatin Interaction ◽

Marker Genes ◽

Systematic Analysis ◽

Genome Wide ◽

Extracellular Stimuli

ABSTRACTBackgroundEndothelial cells (ECs) make up the innermost layer throughout the entire vasculature. Their phenotypes and physiological functions are initially regulated by developmental signals and extracellular stimuli. The underlying molecular mechanisms responsible for the diverse phenotypes of ECs from different organs are not well understood.ResultsTo characterize the transcriptomic and epigenomic landscape in the vascular system, we cataloged gene expression and active histone marks in nine types of human ECs (generating 148 genome-wide datasets) and carried out a comprehensive analysis with chromatin interaction data. We identified 3,765 EC-specific enhancers, some of which were associated with disease-associated genetic variations. We also identified various candidate marker genes for each EC type. Notably, reflecting the developmental origins of ECs and their roles in angiogenesis, vasculogenesis and wound healing.ConclusionsWhile the importance of several HOX genes for early vascular development and adult angiogenesis in pathological conditions has been reported, a systematic analysis of the regulation and roles of HOX genes in mature tissue cells has been lacking. These datasets provide a valuable resource for understanding the vascular system and associated diseases.

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Gene expression profiles during short-term heat stress; branchingvs.massive Scleractinian corals of the Red Sea

PeerJ ◽

10.7717/peerj.1814 ◽

2016 ◽

Vol 4 ◽

pp. e1814 ◽

Cited By ~ 14

Author(s):

Keren Maor-Landaw ◽

Oren Levy

Keyword(s):

Gene Expression ◽

Heat Stress ◽

Redox Regulation ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Expression Patterns ◽

Gene Expression Profiles ◽

Marker Genes ◽

Stylophora Pistillata ◽

Stress Genes

It is well-established that there is a hierarchy of susceptibilities amongst coral genera during heat-stress. However, molecular mechanisms governing these differences are still poorly understood. Here we explored if specific corals possessing different morphologies and different susceptibilities to heat stress may manifest varied gene expression patterns. We examined expression patterns of seven genes in the branching coralsStylophora pistillataandAcropora eurystomaand additionally in the massive robust coral,Poritessp. The tested genes are representatives of key cellular processes occurring during heat-stress in Cnidaria: oxidative stress, ER stress, energy metabolism, DNA repair and apoptosis. Varied response to the heat-stress, in terms of visual coral paling, algal maximum quantum yield and host gene expression was evident in the different growth forms. The two branching corals exhibited similar overall responses that differed from that of the massive coral.A. eurystomathat is considered as a susceptible species did not bleach in our experiment, but tissue sloughing was evident at 34 °C. Interestingly, in this species redox regulation genes were up-regulated at the very onset of the thermal challenge. InS. pistillata, bleaching was evident at 34 °C and most of the stress markers were already up-regulated at 32 °C, either remaining highly expressed or decreasing when temperatures reached 34 °C. The massivePoritesspecies displayed severe bleaching at 32 °C but stress marker genes were only significantly elevated at 34 °C. We postulate that by expelling the algal symbionts fromPoritestissues, oxidation damages are reduced and stress genes are activated only at a progressed stage. The differential gene expression responses exhibited here can be correlated with the literature well-documented hierarchy of susceptibilities amongst coral morphologies and genera in Eilat’s coral reef.

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Spatially resolved transcriptomics reveals unique gene signatures associated with human temporal cortical architecture and Alzheimer's pathology

10.1101/2021.07.07.451554 ◽

2021 ◽

Author(s):

Shuo Chen ◽

Yuzhou Chang ◽

Liangping Li ◽

Diana Acosta ◽

Cody Morrison ◽

...

Keyword(s):

Gene Expression ◽

Single Molecule ◽

Brain Region ◽

Expression Patterns ◽

Middle Temporal Gyrus ◽

Marker Genes ◽

Gene Signatures ◽

Unique Gene ◽

Spatially Resolved ◽

And Gender

Alzheimer's disease (AD) is pathologically characterized by amyloid beta (Aβ) plaques, neurofibrillary tangles (tau aggregates), and alterations in microglia, astrocytes and oligodendrocytes. The mesial temporal lobe is a vulnerable brain region in early AD; however, little is known about the transcriptome-scale gene expression in this region and its relation to AD pathology. Here we use the 10x Genomics Visium platform in combination with co-immunofluorescence staining of AD-associated pathological markers to define the spatial topography of gene expression in the middle temporal gyrus (MTG) from both early AD and age- and gender-matched control cases. We identify unique marker genes for six cortical layers and the adjacent white matter as well as gene expression patterns and alterations that showcase unique gene signatures and pathways associated with a range of AD pathology. Also, gene co-expression analyses of differentially expressed genes (DEGs) between AD and controls reveal four unique gene modules, which significantly change their co-expression patterns in the presence of variations of AD pathology. Furthermore, we validate the changes of key representative DEGs that are associated with AD pathology in neurons, microglia, astrocytes and oligodendrocytes using single-molecule fluorescent in situ hybridization. In summary, we provide a rich resource for the spatial transcriptomic profile of the human MTG, which will contribute to our understanding of the complex architecture and AD pathology of this vulnerable brain region.

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The ETS-Domain Transcription Factor Elk-1 Regulates COX-2 Gene Expression and Inhibits Glucose-Stimulated Insulin Secretion in the Pancreaticβ-Cell Line INS-1

International Journal of Endocrinology ◽

10.1155/2013/843462 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8

Author(s):

Xiong-Fei Zhang ◽

Yi Zhu ◽

Wen-Biao Liang ◽

Jing-Jing Zhang

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Transcriptional Regulation ◽

Insulin Secretion ◽

Cell Line ◽

Molecular Mechanisms ◽

Cell Function ◽

Cell Dysfunction ◽

Cox 2 ◽

Glucose Stimulated Insulin Secretion

Cyclooxygenase-2 (COX-2) expression is associated with many aspects of physiological and pathological conditions, including pancreaticβ-cell dysfunction. Prostaglandin E2 (PGE2) production, as a consequence of COX-2 gene induction, has been reported to impairβ-cell function. The molecular mechanisms involved in the regulation of COX-2 gene expression are not fully understood. We previously demonstrated that transcription factor Elk-1 significantly upregulated COX-2 gene promoter activity. In this report, we used pancreaticβ-cell line (INS-1) to explore the relationships between Elk-1 and COX-2. We first investigated the effects of Elk-1 on COX-2 transcriptional regulation and expression in INS-1 cells. We thus undertook to study the binding of Elk-1 to its putative binding sites in the COX-2 promoter. We also analysed glucose-stimulated insulin secretion (GSIS) in INS-1 cells that overexpressed Elk-1. Our results demonstrate that Elk-1 efficiently upregulates COX-2 expression at least partly through directly binding to the −82/−69 region of COX-2 promoter. Overexpression of Elk-1 inhibits GSIS in INS-1 cells. These findings will be helpful for better understanding the transcriptional regulation of COX-2 in pancreaticβ-cell. Moreover, Elk-1, the transcriptional regulator of COX-2 expression, will be a potential target for the prevention ofβ-cell dysfunction mediated by PGE2.

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Integrative Transcriptomics Reveals Activation of Innate Immune Responses and Inhibition of Inflammation During Oral Immunotherapy for Egg Allergy in Children

Frontiers in Immunology ◽

10.3389/fimmu.2021.704633 ◽

2021 ◽

Vol 12 ◽

Author(s):

Piia Karisola ◽

Kati Palosuo ◽

Victoria Hinkkanen ◽

Lukas Wisgrill ◽

Terhi Savinko ◽

...

Keyword(s):

Gene Expression ◽

Clinical Outcome ◽

Immune Responses ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Oral Immunotherapy ◽

Innate Immune ◽

Egg Allergy ◽

Innate Immune Responses ◽

Open Label

We previously reported the results of a randomized, open-label trial of egg oral immunotherapy (OIT) in 50 children where 44% were desensitized and 46% were partially desensitized after 8 months of treatment. Here we focus on cell-mediated molecular mechanisms driving desensitization during egg OIT. We sought to determine whether changes in genome-wide gene expression in blood cells during egg OIT correlate with humoral responses and the clinical outcome. The blood cell transcriptome of 50 children receiving egg OIT was profiled using peripheral blood mononuclear cell (PBMC) samples obtained at baseline and after 3 and 8 months of OIT. We identified 467 differentially expressed genes (DEGs) after 3 or 8 months of egg OIT. At 8 months, 86% of the DEGs were downregulated and played a role in the signaling of TREM1, IL-6, and IL-17. In correlation analyses, Gal d 1–4-specific IgG4 antibodies associated positively with DEGs playing a role in pathogen recognition and antigen presentation and negatively with DEGs playing a role in the signaling of IL-10, IL-6, and IL-17. Desensitized and partially desensitized patients had differences in their antibody responses, and although most of the transcriptomic changes were shared, both groups had also specific patterns, which suggest slower changes in partially desensitized and activation of NK cells in the desensitized group. OIT for egg allergy in children inhibits inflammation and activates innate immune responses regardless of the clinical outcome at 8 months. Changes in gene expression patterns first appear as posttranslational protein modifications, followed by more sustained epigenetic gene regulatory functions related to successful desensitization.

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Transcriptional regulation in model organisms: recent progress and clinical implications

Open Biology ◽

10.1098/rsob.190183 ◽

2019 ◽

Vol 9 (11) ◽

pp. 190183 ◽

Cited By ~ 14

Author(s):

Jiaqi Tang ◽

Zhenhua Xu ◽

Lianfang Huang ◽

Hui Luo ◽

Xiao Zhu

Keyword(s):

Transcriptional Regulation ◽

Molecular Mechanisms ◽

The Body ◽

Model Organisms ◽

Clinical Implications ◽

Regulation Mechanism ◽

Biological Behaviour ◽

E Coli ◽

Different Types

In this review, we will summarize model organisms used by scientists in the laboratory, including Escherichia coli , yeast, Arabidopsis thaliana , nematodes, Drosophila , zebrafish, mice and other animals. We focus on the progress in research exploring different types of E. coli in the human body, and the specific molecular mechanisms by which they play a role in humans. First, we discuss the specific transcriptional regulation mechanism of E. coli in cell development, maturation, ageing and longevity, as well as tumorigenesis and development. Then, we discuss how the synthesis of some important substances in cells is regulated and how this affects biological behaviour. Understanding and applying these mechanisms, presumably, can greatly improve the quality of people's lives as well as increase their lifespan. For example, some E. coli can activate certain cells by secreting insulin-like growth factor-1, thus activating the inflammatory response of the body, while other E. coli can inactivate the immune response of the body by secreting toxic factors.

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An animal model study on the gene expression profile of meniscal degeneration

Scientific Reports ◽

10.1038/s41598-020-78349-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Yehan Fang ◽

Hui Huang ◽

Gang Zhou ◽

Qinghua Wang ◽

Feng Gao ◽

...

Keyword(s):

Gene Expression ◽

Pathway Analysis ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Control Group ◽

Ion Binding ◽

Endoplasmic Reticulum Membrane ◽

Rt Pcr ◽

Go Analysis ◽

Meniscal Degeneration

AbstractMeniscal degeneration is a very common condition in elderly individuals, but the underlying mechanisms of its occurrence are not completely clear. This study examines the molecular mechanisms of meniscal degeneration. The anterior cruciate ligament (ACL) and lateral collateral ligament (LCL) of the right rear limbs of seven Wuzhishan mini-pigs were resected (meniscal degeneration group), and the left rear legs were sham-operated (control group). After 6 months, samples were taken for gene chip analysis, including differentially expressed gene (DEG) analysis, gene ontology (GO) analysis, clustering analysis, and pathway analysis. The selected 12 DEGs were validated by real time reverse transcription-polymerase chain reaction (RT-PCR). The two groups showed specific and highly clustered DEGs. A total of 893 DEGs were found, in which 537 are upregulated, and 356 are downregulated. The GO analysis showed that the significantly affected biological processes include nitric oxide metabolic process, male sex differentiation, and mesenchymal morphogenesis, the significantly affected cellular components include the endoplasmic reticulum membrane, and the significantly affected molecular functions include transition metal ion binding and iron ion binding. The pathway analysis showed that the significantly affected pathways include type II diabetes mellitus, inflammatory mediator regulation of TRP channels, and AMPK signaling pathway. The results of RT-PCR indicate that the microarray data accurately reflects the gene expression patterns. These findings indicate that several molecular mechanisms are involved in the development of meniscal degeneration, thus improving our understanding of meniscal degeneration and provide molecular therapeutic targets in the future.

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Gene Expression Patterns Underlying the Reinstatement of Plasticity in the Adult Visual System

Neural Plasticity ◽

10.1155/2013/605079 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 11

Author(s):

Ettore Tiraboschi ◽

Ramon Guirado ◽

Dario Greco ◽

Petri Auvinen ◽

Jose Fernando Maya-Vetencourt ◽

...

Keyword(s):

Gene Expression ◽

Visual Cortex ◽

Large Scale ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Monocular Deprivation ◽

Adult Brain ◽

Gene Expression Patterns ◽

Postnatal Life ◽

Critical Periods

The nervous system is highly sensitive to experience during early postnatal life, but this phase of heightened plasticity decreases with age. Recent studies have demonstrated that developmental-like plasticity can be reactivated in the visual cortex of adult animals through environmental or pharmacological manipulations. These findings provide a unique opportunity to study the cellular and molecular mechanisms of adult plasticity. Here we used the monocular deprivation paradigm to investigate large-scale gene expression patterns underlying the reinstatement of plasticity produced by fluoxetine in the adult rat visual cortex. We found changes, confirmed with RT-PCRs, in gene expression in different biological themes, such as chromatin structure remodelling, transcription factors, molecules involved in synaptic plasticity, extracellular matrix, and excitatory and inhibitory neurotransmission. Our findings reveal a key role for several molecules such as the metalloproteases Mmp2 and Mmp9 or the glycoprotein Reelin and open up new insights into the mechanisms underlying the reopening of the critical periods in the adult brain.

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Effects of Cutting, Pruning, and Grafting on the Expression of Age-Related Genes in Larix kaempferi

Forests ◽

10.3390/f11020218 ◽

2020 ◽

Vol 11 (2) ◽

pp. 218

Author(s):

Yao Zhang ◽

Qiao-Lu Zang ◽

Li-Wang Qi ◽

Su-Ying Han ◽

Wan-Feng Li

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Regular Expression ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Reproductive Development ◽

Larix Kaempferi ◽

Clonal Forestry ◽

Cdna Sequences ◽

Age Related

Grafting, cutting, and pruning are important horticultural techniques widely used in the establishment of clonal forestry. After the application of these techniques, some properties of the plants change, however, the underlying molecular mechanisms are still unclear. In our previous study, 27 age-related transcripts were found to be expressed differentially between the juvenile vegetative (1- and 2-year-old) and adult reproductive (25- and 50-year-old) phases of Larix kaempferi. Here, we re-analyzed the 27 age-related transcripts, cloned their full-length cDNA sequences, and measured their responses to grafting, cutting, and pruning. After sequence analysis and cloning, 20 transcription factors were obtained and annotated, most of which were associated with reproductive development, and six (LaAGL2-1, LaAGL2-2, LaAGL2-3, LaSOC1-1, LaAGL11, and LaAP2-2) showed regular expression patterns with L. kaempferi aging. Based on the expression patterns of these transcription factors in L. kaempferi trees subjected to grafting, cutting, and pruning, we concluded that (1) cutting and pruning rejuvenate the plants and change their expression, and the effects of cutting on gene expression are detectable within 14 years, although the cutting seedlings are still maturing during these years; (2) within three months after grafting, the rootstock is more sensitive to grafting than the scion and readily becomes mature with the effect of the scion, while the scion is not readily rejuvenated by the effect of the rootstock; and (3) LaAGL2-2 and LaAGL2-3 are more sensitive to grafting, while LaAP2-2 is impervious to it. These findings not only provide potential molecular markers to assess the state of plants but also aid in studies of the molecular mechanisms of rejuvenation.

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Comparative Genomics and Transcriptomics To Analyze Fruiting Body Development in Filamentous Ascomycetes

Genetics ◽

10.1534/genetics.119.302749 ◽

2019 ◽

Vol 213 (4) ◽

pp. 1545-1563 ◽

Cited By ~ 2

Author(s):

Ramona Lütkenhaus ◽

Stefanie Traeger ◽

Jan Breuer ◽

Laia Carreté ◽

Alan Kuo ◽

...

Keyword(s):

Gene Expression ◽

Fruiting Body ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Regulation Of Gene Expression ◽

Comparative Transcriptomics ◽

Fruiting Bodies ◽

Body Development ◽

Fruiting Body Development ◽

Genes Encoding

Many filamentous ascomycetes develop three-dimensional fruiting bodies for production and dispersal of sexual spores. Fruiting bodies are among the most complex structures differentiated by ascomycetes; however, the molecular mechanisms underlying this process are insufficiently understood. Previous comparative transcriptomics analyses of fruiting body development in different ascomycetes suggested that there might be a core set of genes that are transcriptionally regulated in a similar manner across species. Conserved patterns of gene expression can be indicative of functional relevance, and therefore such a set of genes might constitute promising candidates for functional analyses. In this study, we have sequenced the genome of the Pezizomycete Ascodesmis nigricans, and performed comparative transcriptomics of developing fruiting bodies of this fungus, the Pezizomycete Pyronema confluens, and the Sordariomycete Sordaria macrospora. With only 27 Mb, the A. nigricans genome is the smallest Pezizomycete genome sequenced to date. Comparative transcriptomics indicated that gene expression patterns in developing fruiting bodies of the three species are more similar to each other than to nonsexual hyphae of the same species. An analysis of 83 genes that are upregulated only during fruiting body development in all three species revealed 23 genes encoding proteins with predicted roles in vesicle transport, the endomembrane system, or transport across membranes, and 13 genes encoding proteins with predicted roles in chromatin organization or the regulation of gene expression. Among four genes chosen for functional analysis by deletion in S. macrospora, three were shown to be involved in fruiting body formation, including two predicted chromatin modifier genes.

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