scholarly journals ProbeSelect: selecting differentially expressed probes in transcriptional profile data

2013 ◽  
Vol 30 (4) ◽  
pp. 574-575 ◽  
Author(s):  
Raghavendra Hosur ◽  
Suzanne Szak ◽  
Alice Thai ◽  
Norm Allaire ◽  
Jadwiga Bienkowska
Keyword(s):  
Transcriptional Profile ◽  
Differentially Expressed ◽  
Profile Data

scholarly journals Effect of chronic uremia on the transcriptional profile of the calcified aorta analyzed by RNA sequencing

2016 ◽  
Vol 310 (6) ◽  
pp. F477-F491 ◽  
Author(s):  
Jakob L. Rukov ◽  
Eva Gravesen ◽  
Maria L. Mace ◽  
Jacob Hofman-Bang ◽  
Jeppe Vinther ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Vascular Tissue ◽  
Rat Aorta ◽  
Transcriptional Profile ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Chronic Uremia ◽  
Upregulated Genes ◽  
Calcified Aorta ◽  
First Time

The development of vascular calcification (VC) in chronic uremia (CU) is a tightly regulated process controlled by factors promoting and inhibiting mineralization. Next-generation high-throughput RNA sequencing (RNA-seq) is a powerful and sensitive tool for quantitative gene expression profiling and the detection of differentially expressed genes. In the present study, we, for the first time, used RNA-seq to examine rat aorta transcriptomes from CU rats compared with control rats. Severe VC was induced in CU rats, which lead to extensive changes in the transcriptional profile. Among the 10,153 genes with an expression level of >1 reads/kilobase transcript/million mapped reads, 2,663 genes were differentially expressed with 47% upregulated genes and 53% downregulated genes in uremic rats. Significantly deregulated genes were enriched for ontologies related to the extracellular matrix, response to wounding, organic substance, and ossification. The individually affected genes were of relevance to osteogenic transformation, tissue calcification, and Wnt modulation. Downregulation of the Klotho gene in uremia is believed to be involved in the development of VC, but it is debated whether the effect is caused by circulating Klotho only or if Klotho is produced locally in the vasculature. We found that Klotho was neither expressed in the normal aorta nor calcified aorta by RNA-seq. In conclusion, we demonstrated extensive changes in the transcriptional profile of the uremic calcified aorta, which were consistent with a shift in phenotype from vascular tissue toward an osteochondrocytic transcriptome profile. Moreover, neither the normal vasculature nor calcified vasculature in CU expresses Klotho.

scholarly journals Data MiningMycobacterium tuberculosisPathogenic Gene Transcription Factors and Their Regulatory Network Nodes

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Guangxin Yuan ◽  
Yu Bai ◽  
Yuhang Zhang ◽  
Guangyu Xu
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Expression Profile ◽  
Regulatory Network ◽  
Regulatory Element ◽  
Single Gene ◽  
Differentially Expressed Gene ◽  
Differentially Expressed ◽  
Profile Data ◽  
Extracellular Region

Tuberculosis (TB) is one of the deadliest infectious diseases worldwide. InMycobacterium tuberculosis, changes in gene expression are highly variable and involve many genes, so traditional single-gene screening ofM. tuberculosistargets has been unable to meet the needs of clinical diagnosis. In this study, using the National Center for Biotechnology Information (NCBI) GEO Datasets, whole blood gene expression profile data were obtained in patients with active pulmonary tuberculosis. Linear model-experience Bayesian statistics using the Limma package in R combined witht-tests were applied for nonspecific filtration of the expression profile data, and the differentially expressed human genes were determined. Using DAVID and KEGG, the functional analysis of differentially expressed genes (GO analysis) and the analysis of signaling pathways were performed. Based on the differentially expressed gene, the transcriptional regulatory element databases (TRED) were integrated to construct theM. tuberculosispathogenic gene regulatory network, and the correlation of the network genes with disease was analyzed with the DAVID online annotation tool. It was predicted that IL-6, JUN, and TP53, along with transcription factors SRC, TNF, and MAPK14, could regulate the immune response, with their function being extracellular region activity and protein binding during infection withM. tuberculosis.

scholarly journals Specific Bone Marrow Mesenchymal Subsets in Patients with Myelodysplastic Syndromes Harbor Molecular Perturbations That Alter the Dynamics of Competition between Pre-Leukemic Clones and Normal Cells

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 938-938
Author(s):  
Youmna Kfoury ◽  
Esha Jain ◽  
Jason R Myers ◽  
Fei Ji ◽  
David B Sykes ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Competitive Advantage ◽  
Myelodysplastic Syndromes ◽  
Differentially Expressed Gene ◽  
Mesenchymal Cells ◽  
Transcriptional Profile ◽  
Model Systems ◽  
Differentially Expressed ◽  
Wild Type ◽  
Osteoprogenitor Cells

Abstract Myelodysplastic syndromes (MDS) are clonal disorders of aberrant hematopoietic stem cells. The role of the hematopoietic microenvironment (HMEV) in the initiation and maintenance of MDS remains unclear, though model systems have provided strong evidence for the potential of specific mesenchymal subsets, mostly osteoprogenitor cells, within the HMEV as a driver of the disease. Distinct behavior of various models emphasizes the importance of analyzing specific and highly defined populations rather than bulk mesenchymal cells when investigating patient-derived bone marrow (BM) samples. We have developed a platform that allows us to prospectively isolate specific human BM mesenchymal subsets with a comparable transcriptional profile to mouse osteoprogenitor cells that have been shown to drive hematological malignancies when perturbed (Raaijmakers et al., 2010; Dong et al, 2016). Using a combination of three cell surface markers (CD271, CD146, CD106) that were previously shown to prospectively enrich for mesenchymal cells in human BM, we isolated and performed transcriptional and functional analysis of four distinct subsets within the non-hematopoietic (CD45, CD235), non-endothelial (CD31) compartment of the human BM. The four populations are labeled 1A (CD271+CD106-), 1B (CD271+CD106+), 2A (CD271+CD146+CD106-), and 2B (CD271+CD146+CD106+) (Figure 1A). Comparative analysis of differentially expressed gene sets based on RNA-seq within the human and mouse mesenchymal populations identified population 2B to be the most similar to osterix (OSX)-labeled mouse osteoprogenitor cells, whereas population 1A was more similar to osteocalcin (OCN)-labeled mouse mature osteoblasts. In animal models, genetic perturbations specifically in OSX but not OCN labeled cells resulted in hematological malignancy. Based on that observation, we hypothesized that population 2B is the cell subset most likely to harbor molecular perturbations in the BM of MDS patients. We analyzed populations 2A, 2B, 1(1A+1B) and another population 3 which is devoid of colony forming cells and encompasses all CD271-CD146- non hematopoietic stromal cells in 16 human MDS patients. BM from 11 patients undergoing hip replacement surgeries was used as a source of age- and gender-matched normal controls. Despite the heterogeneity of the disease, principal component analysis revealed that the transcriptional profile of normal samples clearly separated from MDS patients mostly in populations 2B and 1 (Figure 1B). Functional annotation of the differentially expressed genes using the Database for Annotation, Visualization and Integrated Discovery (DAVID) demonstrated minimal overlap of enriched terms between the four populations. Thus our data demonstrate transcriptionally distinct subsets of BM mesenchymal cells and identify signatures of transcriptional deregulation which differentiate these cell subsets in MDS patients from normal individuals. Osteopontin, an extracellular matrix protein expressed by osteoblasts among other cells, was the most significantly differentially expressed gene in population 2B of MDS patients.To study the effect of the gene expression perturbations on MDS evolution in vivo, we created a chimeric model where BM cells expressing the Nup98/HoxD13 (NHD13) translocation were transplanted in competition with wild type cells in wild type (WT) or osteopontin knock out (Opn-KO) recipients. Animals were conditioned using immunotoxin to avoid the damaging effect of irradiation on the microenvironment. Following chimerism of donor cells in peripheral blood over 24 weeks demonstrated a competitive advantage of NHD13 cells in the Opn-KO recipients leading to a significant difference in survival when compared to NHD13 cells transplanted in wild type mice (Figure 1C, D). Altogether, our data provide evidence that specific mesenchymal progenitor subsets in the BM of MDS patients harbor molecular perturbations that contribute to the competitive advantage of MDS over normal hematopoietic cells. Disclosures Sykes: Clear Creek Bio: Equity Ownership, Other: Co-founder.

3 Modulation of glycolysis alters histone acetylation and gene expression in bovine blastocysts produced invitro

2021 ◽  
Vol 33 (2) ◽  
pp. 109
Author(s):  
A. M. Fonseca Junior ◽  
E. E. Paulson ◽  
D. E. Goszczynski ◽  
J. Ispada ◽  
E. C. Santos ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Energy Metabolism ◽  
Histone Acetylation ◽  
Nucleotide Metabolism ◽  
Transcriptional Profile ◽  
Differentially Expressed ◽  
Mitochondrial Activity ◽  
Rna Seq ◽  
Acetyl Coa ◽  
Atp Levels

Changes in the dynamics of energy metabolism can affect the sophisticated molecular control of different cell types including embryonic stem cells (Zhang et al. 2018 Cell Metab. 27, 332-338; https://doi.org/10.1016/j.cmet.2018.01.008). In this study, we modulated pathways related to acetyl-CoA generation, the major donor for histone acetylation, and explored how this affects histone acetylation and the transcriptional profile of bovine blastocysts. Embryos were produced invitro by conventional protocols. On Day 4 of culture (Fertilization=Day 0), embryos were randomly allocated into 3 experimental groups according to culture medium [synthetic oviductal fluid with amino acids (SOFaa) + 4% bovine serum albumin] supplementation: Control (no additional supplementation), sodium iodoacetate (IA; 2 µM; glycolysis inhibitor), and sodium dichloroacetate (DCA; 2 mM; acetyl-CoA conversion stimulator). Expanded blastocysts were collected on Day 7 and assessed for ATP levels (luminescence), mitochondrial activity (MitoTracker Red CMXRos; ThermoFisher Scientific), histone 3 lysine 9 and 27 acetylation (H3K9ac and H3K27ac; immunostaining) and transcriptional profiling by RNA sequencing (RNA-Seq) of isolated inner cell mass. Data were submitted to normality test and treatment groups were compared to control using t-test or Mann–Whitney test for non-parametric data (mean±s.e.) considering P<0.05. RNA-Seq data were analysed by DESEqn 2 and transcripts with Padj <0.05 were submitted to gene ontology by DAVID (https://david.ncifcrf.gov/). Mitochondrial activity was higher in DCA compared with Control (control: 53078±2747 AU vs. DCA: 57520±902 AU; P=0.0034), which explains the higher ATP levels found in this group (control: 1.49±0.65 µM vs. DCA: 41.56±15.69 µM; P=0.03). However, although mitochondrial activity was expectedly lower in IA compared to control (control: 53078±2747 A.U. vs. DCA: 36249±3200 A.U.; P=0.0013), we did not observe a decrease in ATP levels (control: 1.49±0.65µM vs. IA: 3.23±1.13 µM; P=0.12). Confirming our hypothesis, modulation of acetyl-CoA generation affected histone acetylation, with levels of H3K9ac and H3K27ac being higher in DCA and lower in IA compared with Control (H3K9ac Control: 988.3±22.82 AU, DCA: 1301±32.28 AU, IA: 684±23.7 AU; P<0.0001 and H3K27ac Control: 502.5±13.64 AU, DCA: 667.2±12.19 AU, IA: 417.2±12.03 AU; P<0.0001). Finally, 905 genes were differentially expressed, 599 up- and 306 downregulated in DCA compared with Control. Another 675 genes were differentially expressed between control and IA, (385 up- and 290 downregulated in IA). Gene ontology indicated that, compared with control, the biological functions upregulated in DCA were related to developmental process and the downregulated functions were associated with metabolism regulation, indicating a role of metabolic pathways in the developmental competence of the embryo. IA, in contrast, had catabolic activity upregulated and nucleotide metabolism downregulated compared with control, supporting the depletion of metabolic activity and lower acetylation. Taken together, our results demonstrate that the modulation of energy metabolism affects the epigenetic status of bovine embryos with consequences for the transcriptional profile of pathways involved in embryo quality and viability.

Differentially expressed microRNAs during myofibroblastic transdifferentiation of Hepatic Stellate Cells

2009 ◽  
Vol 47 (01) ◽  
Author(s):  
I Strack ◽  
M Scheffler ◽  
S Schievenbusch ◽  
J Riemer ◽  
A Noetel ◽  
...  
Keyword(s):  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Differentially Expressed
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