Impact of Gene Dosage on Gene Expression, Biological Processes and Survival in Cervical Cancer: A Genome-Wide Follow-Up Study

AbstractMaternal postpartum depression (PPD) is a significant public health concern due to the severe negative impact on maternal and child health and well-being. In this study, we aimed to identify genes associated with PPD. To do this, we investigated genome-wide gene expression profiles of pregnant women during their third trimester of pregnancy and tested the association of gene expression with perinatal depressive symptoms. A total of 137 women from a cohort from the University of North Carolina, USA were assessed. The main phenotypes analysed were Edinburgh Postnatal Depression Scale (EPDS) scores at 2 months postpartum and PPD (binary yes/no) based on an EPDS cutoff of 10. Illumina NextSeq500/550 transcriptomic sequencing from whole blood was analysed using the edgeR package. We identified 71 genes significantly associated with postpartum depression scores at 2 months, after correction for multiple testing at 5% FDR. These included several interesting candidates including TNFRSF17, previously reported to be significantly upregulated in women with PPD and MMP8, a matrix metalloproteinase gene, associated with depression in a genome-wide association study. Functional annotation of differentially expressed genes revealed an enrichment of immune response-related biological processes. Additional analysis of genes associated with changes in depressive symptoms from recruitment to 2 months postpartum identified 66 genes significant at an FDR of 5%. Of these genes, 33 genes were also associated with depressive symptoms at 2 months postpartum. Comparing the results with previous studies, we observed that 15.4% of genes associated with PPD in this study overlapped with 700 core maternal genes that showed significant gene expression changes across multiple brain regions (P = 7.9e-05) and 29–53% of the genes were also associated with estradiol changes in a pharmacological model of depression (P values range = 1.2e-4–2.1e-14). In conclusion, we identified novel genes and validated genes previously associated with oestrogen sensitivity in PPD. These results point towards the role of an altered immune transcriptomic landscape as a vulnerability factor for PPD.

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A genome-wide transcriptomic analysis of embryos fathered by obese males in a murine model of diet-induced obesity

Scientific Reports ◽

10.1038/s41598-021-81226-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Laura Bernhardt ◽

Marcus Dittrich ◽

Rabih El-Merahbi ◽

Antoine-Emmanuel Saliba ◽

Tobias Müller ◽

...

Keyword(s):

Gene Expression ◽

Negative Impact ◽

Preimplantation Embryos ◽

High Fat ◽

Cell Stage ◽

Genetic Transmission ◽

Diet Induced Obesity ◽

Genome Wide ◽

A Genome ◽

Paternal Obesity

AbstractPaternal obesity is known to have a negative impact on the male’s reproductive health as well as the health of his offspring. Although epigenetic mechanisms have been implicated in the non-genetic transmission of acquired traits, the effect of paternal obesity on gene expression in the preimplantation embryo has not been fully studied. To this end, we investigated whether paternal obesity is associated with gene expression changes in eight-cell stage embryos fathered by males on a high-fat diet. We used single embryo RNA-seq to compare the gene expression profile of embryos generated by males on a high fat (HFD) versus control (CD) diet. This analysis revealed significant upregulation of the Samd4b and Gata6 gene in embryos in response to a paternal HFD. Furthermore, we could show a significant increase in expression of both Gata6 and Samd4b during differentiation of stromal vascular cells into mature adipocytes. These findings suggest that paternal obesity may induce changes in the male germ cells which are associated with the gene expression changes in the resulting preimplantation embryos.

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DNA Methylation at ATP11A cg11702988 Is a Biomarker of Lung Disease Severity in Cystic Fibrosis: A Longitudinal Study

Genes ◽

10.3390/genes12030441 ◽

2021 ◽

Vol 12 (3) ◽

pp. 441

Author(s):

Fanny Pineau ◽

Davide Caimmi ◽

Sylvie Taviaux ◽

Maurane Reveil ◽

Laura Brosseau ◽

...

Keyword(s):

Cystic Fibrosis ◽

Dna Methylation ◽

Clinical Trials ◽

Lung Disease ◽

Disease Severity ◽

Genome Wide ◽

A Genome ◽

Lung Disease Severity ◽

Epigenetic Biomarker

Cystic fibrosis (CF) is a chronic genetic disease that mainly affects the respiratory and gastrointestinal systems. No curative treatments are available, but the follow-up in specialized centers has greatly improved the patient life expectancy. Robust biomarkers are required to monitor the disease, guide treatments, stratify patients, and provide outcome measures in clinical trials. In the present study, we outline a strategy to select putative DNA methylation biomarkers of lung disease severity in cystic fibrosis patients. In the discovery step, we selected seven potential biomarkers using a genome-wide DNA methylation dataset that we generated in nasal epithelial samples from the MethylCF cohort. In the replication step, we assessed the same biomarkers using sputum cell samples from the MethylBiomark cohort. Of interest, DNA methylation at the cg11702988 site (ATP11A gene) positively correlated with lung function and BMI, and negatively correlated with lung disease severity, P. aeruginosa chronic infection, and the number of exacerbations. These results were replicated in prospective sputum samples collected at four time points within an 18-month period and longitudinally. To conclude, (i) we identified a DNA methylation biomarker that correlates with CF severity, (ii) we provided a method to easily assess this biomarker, and (iii) we carried out the first longitudinal analysis of DNA methylation in CF patients. This new epigenetic biomarker could be used to stratify CF patients in clinical trials.

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A Genome-Wide Integrative Association Study of DNA Methylation and Gene Expression Data and Later Life Cognitive Functioning in Monozygotic Twins

Frontiers in Neuroscience ◽

10.3389/fnins.2020.00233 ◽

2020 ◽

Vol 14 ◽

Cited By ~ 1

Author(s):

Mette Soerensen ◽

Dominika Marzena Hozakowska-Roszkowska ◽

Marianne Nygaard ◽

Martin J. Larsen ◽

Veit Schwämmle ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Cognitive Functioning ◽

Association Study ◽

Gene Expression Data ◽

Monozygotic Twins ◽

Later Life ◽

Expression Data ◽

Genome Wide ◽

A Genome

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Genome-wide identification and characterization of long non-coding RNAs involved in flag leaf senescence of rice

Plant Molecular Biology ◽

10.1007/s11103-021-01121-3 ◽

2021 ◽

Author(s):

Xiaoping Huang ◽

Hongyu Zhang ◽

Qiang Wang ◽

Rong Guo ◽

Lingxia Wei ◽

...

Keyword(s):

Transcription Factors ◽

Leaf Senescence ◽

Flag Leaf ◽

Reduction Process ◽

Sequencing Analysis ◽

Biological Processes ◽

Genome Wide ◽

A Genome ◽

Non Coding Rnas ◽

Systematic Identification

Abstract Key message This study showed the systematic identification of long non-coding RNAs (lncRNAs) involving in flag leaf senescence of rice, providing the possible lncRNA-mRNA regulatory relationships and lncRNA-miRNA-mRNA ceRNA networks during leaf senescence. Abstract LncRNAs have been reported to play crucial roles in diverse biological processes. However, no systematic identification of lncRNAs associated with leaf senescence in plants has been studied. In this study, a genome-wide high throughput sequencing analysis was performed using rice flag leaves developing from normal to senescence. A total of 3953 lncRNAs and 38757 mRNAs were identified, of which 343 lncRNAs and 9412 mRNAs were differentially expressed. Through weighted gene co-expression network analysis (WGCNA), 22 continuously down-expressed lncRNAs targeting 812 co-expressed mRNAs and 48 continuously up-expressed lncRNAs targeting 1209 co-expressed mRNAs were considered to be significantly associated with flag leaf senescence. Gene Ontology results suggested that the senescence-associated lncRNAs targeted mRNAs involving in many biological processes, including transcription, hormone response, oxidation–reduction process and substance metabolism. Additionally, 43 senescence-associated lncRNAs were predicted to target 111 co-expressed transcription factors. Interestingly, 8 down-expressed lncRNAs and 29 up-expressed lncRNAs were found to separately target 12 and 20 well-studied senescence-associated genes (SAGs). Furthermore, analysis on the competing endogenous RNA (CeRNA) network revealed that 6 down-expressed lncRNAs possibly regulated 51 co-expressed mRNAs through 15 miRNAs, and 14 up-expressed lncRNAs possibly regulated 117 co-expressed mRNAs through 21 miRNAs. Importantly, by expression validation, a conserved miR164-NAC regulatory pathway was found to be possibly involved in leaf senescence, where lncRNA MSTRG.62092.1 may serve as a ceRNA binding with miR164a and miR164e to regulate three transcription factors. And two key lncRNAs MSTRG.31014.21 and MSTRG.31014.36 also could regulate the abscisic-acid biosynthetic gene BGIOSGA025169 (OsNCED4) and BGIOSGA016313 (NAC family) through osa-miR5809. The possible regulation networks of lncRNAs involving in leaf senescence were discussed, and several candidate lncRNAs were recommended for prior transgenic analysis. These findings will extend the understanding on the regulatory roles of lncRNAs in leaf senescence, and lay a foundation for functional research on candidate lncRNAs.

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Co-Overexpression of TWIST1-CSF1 Is a Common Event in Metastatic Oral Cancer and Drives Biologically Aggressive Phenotype

Cancers ◽

10.3390/cancers13010153 ◽

2021 ◽

Vol 13 (1) ◽

pp. 153

Author(s):

Sabrina Daniela da Silva ◽

Fabio Albuquerque Marchi ◽

Jie Su ◽

Long Yang ◽

Ludmila Valverde ◽

...

Keyword(s):

Epithelial Mesenchymal Transition ◽

Inflammatory Cells ◽

Rank Test ◽

Mesenchymal Transition ◽

Genome Wide ◽

A Genome ◽

Enhanced Expression ◽

Advanced Stages

Invasive oral squamous cell carcinoma (OSCC) is often ulcerated and heavily infiltrated by pro-inflammatory cells. We conducted a genome-wide profiling of tissues from OSCC patients (early versus advanced stages) with 10 years follow-up. Co-amplification and co-overexpression of TWIST1, a transcriptional activator of epithelial-mesenchymal-transition (EMT), and colony-stimulating factor-1 (CSF1), a major chemotactic agent for tumor-associated macrophages (TAMs), were observed in metastatic OSCC cases. The overexpression of these markers strongly predicted poor patient survival (log-rank test, p = 0.0035 and p = 0.0219). Protein analysis confirmed the enhanced expression of TWIST1 and CSF1 in metastatic tissues. In preclinical models using OSCC cell lines, macrophages, and an in vivo matrigel plug assay, we demonstrated that TWIST1 gene overexpression induces the activation of CSF1 while TWIST1 gene silencing down-regulates CSF1 preventing OSCC invasion. Furthermore, excessive macrophage activation and polarization was observed in co-culture system involving OSCC cells overexpressing TWIST1. In summary, this study provides insight into the cooperation between TWIST1 transcription factor and CSF1 to promote OSCC invasiveness and opens up the potential therapeutic utility of currently developed antibodies and small molecules targeting cancer-associated macrophages.

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