scholarly journals Chromosome Missegregation in Single Human Oocytes Is Related to the Age and Gene Expression Profile

2020 ◽  
Vol 21 (6) ◽  
pp. 1934 ◽  
Author(s):  
Stefano Barone ◽  
Patrizia Sarogni ◽  
Roberto Valli ◽  
Maria Michela Pallotta ◽  
Gazzi Silvia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Basis ◽  
Cumulus Cells ◽  
Comparative Genomic ◽  
Transcription Profile ◽  
Human Oocytes ◽  
Cytoskeleton Organization ◽  
Chromosome Missegregation ◽  
Age Related ◽  
Insight Into

The growing trend for women to postpone childbearing has resulted in a dramatic increase in the incidence of aneuploid pregnancies. Despite the importance to human reproductive health, the events precipitating female age-related meiotic errors are poorly understood. To gain new insight into the molecular basis of age-related chromosome missegregation in human oocytes, we combined the transcriptome profiles of twenty single oocytes (derived from females divided into two groups according to age <35 and ≥35 years) with their chromosome status obtained by array comparative genomic hybridization (aCGH). Furthermore, we compared the transcription profile of the single oocyte with the surrounding cumulus cells (CCs). RNA-seq data showed differences in gene expression between young and old oocytes. Dysregulated genes play a role in important biological processes such as gene transcription regulation, cytoskeleton organization, pathways related to RNA maturation and translation. The comparison of the transcription profile of the oocyte and the corresponding CCs highlighted the differential expression of genes belonging to the G protein-coupled receptor superfamily. Finally, we detected the loss of a X chromosome in two oocytes derived from women belonging to the ≥35 years age group. These aneuploidies may be caused by the detriment of REEP4, an endoplasmic reticulum protein, in women aged ≥35 years. Here we gained new insight into the complex regulatory circuit between the oocyte and the surrounding CCs and uncovered a new putative molecular basis of age-related chromosome missegregation in human oocytes.

Expression profiles of select genes in cumulus–oocyte complexes from young and aged mares

2015 ◽  
Vol 27 (6) ◽  
pp. 914 ◽  
Author(s):  
Lindsay Cox ◽  
Dirk K. Vanderwall ◽  
Kate C. Parkinson ◽  
Alexis Sweat ◽  
S. Clay Isom
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cumulus Cells ◽  
Developmental Competence ◽  
Differentially Expressed ◽  
Initiation Factor ◽  
Translational Initiation ◽  
Human Oocytes ◽  
Age Related

There is compelling evidence that oocytes from mares >18 years of age have a high incidence of inherent defects that result in early embryonic loss. In women, an age-related decrease in oocyte quality is associated with an increased incidence of aneuploidy and it has recently been determined that the gene expression profile of human oocytes is altered with advancing age. We hypothesised that similar age-related aberrations in gene expression occur in equine oocytes. Therefore, the aim of the present study was to compare gene expression profiles of individual oocytes and cumulus cells from young and aged mares, specifically evaluating genes that have been identified as being differentially expressed with advancing maternal age and/or aneuploidy in human oocytes. Expression of 48 genes was compared between 14 cumulus–oocyte complexes (COCs) from mares aged 3–12 years and 10 COCs from mares ≥18 years of age. Three genes (mitochondrial translational initiation factor 3 (IF3), heat shock transcription factor 5 (HSF5) and Y box binding protein 2 (YBX2)) were differentially expressed in oocytes, with all being more abundant in oocytes from young mares. Three genes (ADP-ribosylation factor-like 6 interacting protein 6 (ARL6IP6), BCL2-associated X protein (BAX) and hypoxia upregulated 1 (HYOU1)) were differentially expressed in cumulus cells, with all being more abundant in aged mares. The results of the present study confirm there are age-related differences in gene expression in equine COCs, which may be associated with the lower quality and decreased developmental competence of oocytes from aged mares.

An Integrated Epigenomic Analysis Approach To Determine the Molecular Basis of Acute Leukemias.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3276-3276
Author(s):  
Maria E. Figueroa ◽  
Kenny M. Ye ◽  
Elisabeth Paietta ◽  
John M. Greally ◽  
Ari M. Melnick
Keyword(s):  
Gene Expression ◽  
Molecular Basis ◽  
Expression Profiles ◽  
Gene Activity ◽  
Gene Copy ◽  
Comparative Genomic ◽  
Acute Leukemias ◽  
Expression Arrays ◽  
Genome Wide ◽  
Depth Analysis

Abstract Acute leukemias are classified based on their immunologic, cytogenetic and morphologic characteristics. However, in most instances, response to treatment and survival probability cannot be accurately predicted, suggesting that the disease is even more complex and heterogeneous than can be shown with current techniques. Although prognostic value has been shown for certain gene expression profiles, expression profile studies are limited by the fact that only a snapshot of mRNA content is obtained in a basal state, failing to represent how genes will respond to different stresses, also failing to detect the roles of genes expressed at lower levels for which major changes in expression levels are often lost in the “noise” of expression arrays. In order to overcome these issues and to provide a more accurate molecular phenotype of acute leukemias, we established an integrated epigenomic and genomic high-throughput platform using novel techniques and custom high-density oligonucleotide arrays. We combine studies of i) genome-wide cytosine methylation using a novel technique we developed that provides accurate quantitative determination of DNA methylation levels, using genome-wide custom oligo arrays, ii) chromatin structure by ChIP on chip for histone code settings associated with active or repressed genes using 24 K promoter tiling arrays, iii) gene copy number by array-based comparative genomic hybridization (array CGH) at 6 kb resolution genome-wide and iv) 36 K gene expression arrays. Results are validated by single locus quantitative PCR techniques. Cross platform integration is facilitated by use of NimbleGen oligo arrays for all studies and analysis using novel bioinformatics and statistical models. We used this integrative analysis platform to perform an in-depth analysis of the epigenomic basis of AML and ALL using primary patient samples and cell lines. The data allowed us to generate a “gene activity index” which identified the ability of genes to be expressed to be characterized genome-wide in AML and ALL cells. This data also allowed a much more comprehensive analysis of pathways active in these cells to be identified in comparison to expression arrays alone. Our current studies apply integrative platform and gene activity indexing to large series of patients enrolled in multicenter clinical trials in order to provide high-resolution analysis of the molecular basis of acute leukemia.

Genetic Abnormalities Involved in the Development and Progression of Follicular Lymphoma.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2049-2049
Author(s):  
Karen E Deffenbacher ◽  
George Wright ◽  
Javeed Iqbal ◽  
Huimin Geng ◽  
Derville O’Shea ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Resolution ◽  
Follicular Lymphoma ◽  
Copy Number ◽  
Clinical Course ◽  
B Cell Lymphoma ◽  
Genetic Alterations ◽  
Comparative Genomic ◽  
Oncogenic Pathways ◽  
Insight Into

Abstract Background: Follicular lymphoma (FL) is the most common indolent B-cell lymphoma and remains incurable by current therapeutic approaches. Clinical course is variable, and transformation into an aggressive lymphoma (t-FL) with marked worsening of prognosis occurs in 20–60% of patients. While Bcl2 gene translocation is a critical initiating event in the majority of FL cases, evidence indicates it is not sufficient for the development of a FL. Characterization of the genetic alterations subsequent to Bcl2 translocation will lend insight into the oncogenic pathways that contribute to FL pathogenesis and the molecular mechanisms underlying variability in clinical course. Methods: To define recurrent genomic copy number alterations (CNA) in FL, we performed high resolution array comparative genomic hybridization (aCGH) using the Affymetrix 500K SNP array platform. aCGH data were generated on a series of 112 FL cases with available gene expression profiling (GEP) and clinical information. Gene expression data were correlated with copy number data using the Gene Expression and Dosage Integrator (GEDI) algorithm developed at the NCI. Results: Selecting for abnormalities occurring in &gt;10% of cases, the minimal common region (MCR) for 38 losses and 31 gains were defined. Novel common regions included gains on 15q11, 16p11, 5p14 and 19q13, and losses on 3q29, and 16p13. The MCR identified by aCGH were also compared with our existing cytogenetic data on 360 FL cases. MCR residing within the most frequent cytogenetic imbalances (&gt;5%) were selected for analysis at the gene level to further refine these regions. These include gains on 1q21, 2p16, 7q11, 8q24, 12q13, 17q21, 18q21, 21q11, and X, and losses on 1p36, 6q, 10q, 13q34, and 17p13. Recurrent amplifications were detected for the 2p16, 15q11, and 17q21 MCR, while frequent uniparental disomy (UPD) was found to overlap the region of loss on 1p36. Recurrent UPD was also noted on 6p, 12q, 15q and 16p. For the majority of selected MCR, global expression of the genes residing in the MCR demonstrated an association with copy number status. Within these abnormalities, individual genes showing significant correlation with copy number were also identified. Conclusion: The combination of high resolution aCGH and GEP facilitated the identification of functionally relevant genes within the chromosomal abnormalities in FL. Delineation of these molecular targets will provide insight into the oncogenic pathways that contribute to FL disease pathogenesis and may provide novel therapeutic targets.

scholarly journals Age-related gene expression profiles of immature human oocytes

2018 ◽  
Vol 24 (10) ◽  
pp. 469-477 ◽  
Author(s):  
M A J Smits ◽  
K M Wong ◽  
E Mantikou ◽  
C M Korver ◽  
A Jongejan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Related Gene ◽  
Human Oocytes ◽  
Age Related

scholarly journals Molecular basis for clinical diversity between autoantibody subsets in diffuse cutaneous systemic sclerosis

2021 ◽  
pp. annrheumdis-2021-220402
Author(s):  
Kristina Elizabeth Neergaard Clark ◽  
Corrado Campochiaro ◽  
Eszter Csomor ◽  
Adam Taylor ◽  
Katherine Nevin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Sclerosis ◽  
Serum Protein ◽  
Molecular Basis ◽  
Expression Profiles ◽  
Rna Polymerase Iii ◽  
Gene Expression Profiles ◽  
Longitudinal Change ◽  
Protein Markers ◽  
Insight Into

ObjectivesClinical heterogeneity is a cardinal feature of systemic sclerosis (SSc). Hallmark SSc autoantibodies are central to diagnosis and associate with distinct patterns of skin-based and organ-based complications. Understanding molecular differences between patients will benefit clinical practice and research and give insight into pathogenesis of the disease. We aimed to improve understanding of the molecular differences between key diffuse cutaneous SSc subgroups as defined by their SSc-specific autoantibodiesMethodsWe have used high-dimensional transcriptional and proteomic analysis of blood and the skin in a well-characterised cohort of SSc (n=52) and healthy controls (n=16) to understand the molecular basis of clinical diversity in SSc and explore differences between the hallmark antinuclear autoantibody (ANA) reactivities.ResultsOur data define a molecular spectrum of SSc based on skin gene expression and serum protein analysis, reflecting recognised clinical subgroups. Moreover, we show that antitopoisomerase-1 antibodies and anti-RNA polymerase III antibodies specificities associate with remarkably different longitudinal change in serum protein markers of fibrosis and divergent gene expression profiles. Overlapping and distinct disease processes are defined using individual patient pathway analysis.ConclusionsOur findings provide insight into clinical diversity and imply pathogenetic differences between ANA-based subgroups. This supports stratification of SSc cases by ANA antibody subtype in clinical trials and may explain different outcomes across ANA subgroups in trials targeting specific pathogenic mechanisms.

Nanoparticle-plasma Membrane Interactions: Thermodynamics, Toxicity and Cellular Response

2020 ◽  
Vol 27 (20) ◽  
pp. 3330-3345
Author(s):  
Ana G. Rodríguez-Hernández ◽  
Rafael Vazquez-Duhalt ◽  
Alejandro Huerta-Saquero
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Cellular Response ◽  
Cellular Level ◽  
Membrane Interactions ◽  
Daily Lives ◽  
Cellular Physiology ◽  
Associated Proteins ◽  
First Contact ◽  
Insight Into

Nanomaterials have become part of our daily lives, particularly nanoparticles contained in food, water, cosmetics, additives and textiles. Nanoparticles interact with organisms at the cellular level. The cell membrane is the first protective barrier against the potential toxic effect of nanoparticles. This first contact, including the interaction between the cell membranes -and associated proteins- and the nanoparticles is critically reviewed here. Nanoparticles, depending on their toxicity, can cause cellular physiology alterations, such as a disruption in cell signaling or changes in gene expression and they can trigger immune responses and even apoptosis. Additionally, the fundamental thermodynamics behind the nanoparticle-membrane and nanoparticle-proteins-membrane interactions are discussed. The analysis is intended to increase our insight into the mechanisms involved in these interactions. Finally, consequences are reviewed and discussed.

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