scholarly journals Integrative analyses of gene expression profile reveal potential crucial roles of mitotic cell cycle and microtubule cytoskeleton in pulmonary artery hypertension

2019 ◽  
Author(s):  
Jing Luo ◽  
Zhenwei Liu ◽  
Chenlu Li ◽  
Ruochen Wang ◽  
Jinxia Fang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Mitotic Cell ◽  
Functional Enrichment ◽  
Mitotic Cell Cycle ◽  
Public Database ◽  
Hub Genes ◽  
Microtubule Cytoskeleton

Abstract Background: Pulmonary arterial hypertension (PAH) is a life-threatening condition that gets worse over time. Despite advances in the development of strategies for treating PAH, prognosis of the disease remains unsatisfactory, especially for advanced PAH. The aim of this study was to explore potential crucial genes and pathways associated with PAH that can be used as potential biomarkers for early diagnosis.Results: Gene expression profile of pulmonary tissues from 27 PAH patients and 22 normal controls were downloaded from public database (GSE53408 and GSE113439). A total of 521 differentially expressed genes (DEGs), including 432 up-regulated DEGs and 89 down-regulated DEGs were identified using “limma” package in R. Functional enrichment analysis showed that these DEGs were mainly enriched in mitotic cell cycle process, mitotic cell cycle and microtubule cytoskeleton organization. Moreover, five key genes (CDK1, SMC2, SMC4, KIF23, and CENPE) were identified based on the comprehensive evaluation of PPI analysis, modular analysis and cytohubba’s analysis, then further validated in another transcriptomic data set associated with PAH from public database (GSE33463). Furthermore, these hub genes were mainly enriched in promoting mitotic cell cycle process, which may be closely associated with the pathogenesis of PAH. We also found that the predicted miRNAs targeting these hub genes were found to be enriched in TGF-β and Hippo signaling pathway.Conclusion: These findings are expected to gain a further insight into the development of PAH and provide a promising index for the detection of PAH.

scholarly journals Integrative analyses of gene expression profile reveal potential crucial roles of mitotic cell cycle and microtubule cytoskeleton in pulmonary artery hypertension

2020 ◽  
Author(s):  
Jing Luo ◽  
Zhenwei Liu ◽  
Chenlu Li ◽  
Ruochen Wang ◽  
Jinxia Fang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Mitotic Cell ◽  
Mitotic Cell Cycle ◽  
Public Database ◽  
Hub Genes ◽  
Microtubule Cytoskeleton ◽  
Integrative Analyses

Abstract Background: Pulmonary arterial hypertension (PAH) is a life-threatening condition that gets worse over time. Despite advances in the development of strategies for treating PAH, prognosis of the disease remains unsatisfactory, especially for advanced PAH. The aim of this study was to explore potential crucial genes and pathways associated with PAH based on integrative analyses of gene expression and shed light on the identification of biomarker for PAH. Results: Gene expression profile of pulmonary tissues from 27 PAH patients and 22 normal controls were downloaded from public database (GSE53408 and GSE113439). A total of 521 differentially expressed genes (DEGs), including 432 up-regulated DEGs and 89 down-regulated DEGs were identified using “limma” package in R. Functional enrichment analysis showed that these DEGs were mainly enriched in mitotic cell cycle process, mitotic cell cycle and microtubule cytoskeleton organization. Moreover, five key genes (CDK1, SMC2, SMC4, KIF23, and CENPE) were identified based on the comprehensive evaluation of protein-protein interaction (PPI) network analysis, modular analysis and cytohubba’s analysis, then further validated in another transcriptomic data set associated with PAH from public database (GSE33463). Furthermore, these hub genes were mainly enriched in promoting mitotic cell cycle process, which may be closely associated with the pathogenesis of PAH. We also found that the predicted micro-RNAs (miRNAs) targeting these hub genes were found to be enriched in TGF-β and Hippo signaling pathway. Conclusion:These findings are expected to gain a further insight into the development of PAH and provide a promising index for the detection of PAH.

Induction of yeast histone genes by stimulation of stationary-phase cells

1990 ◽  
Vol 10 (12) ◽  
pp. 6356-6361
Author(s):  
M A Drebot ◽  
L M Veinot-Drebot ◽  
R A Singer ◽  
G C Johnston
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Stationary Phase ◽  
Mitotic Cell ◽  
Specific Gene ◽  
Mitotic Cell Cycle ◽  
Histone Genes ◽  
Yeast Saccharomyces Cerevisiae ◽  
Alpha Factor ◽  
Stimulation Of

In the cell cycle of the budding yeast Saccharomyces cerevisiae, expression of the histone genes H2A and H2B of the TRT1 and TRT2 loci is regulated by the performance of "start," the step that also regulates the cell cycle. Here we show that histone production is also subject to an additional form of regulation that is unrelated to the mitotic cell cycle. Expression of histone genes, as assessed by Northern (RNA) analysis, was shown to increase promptly after the stimulation, brought about by fresh medium, that activates stationary-phase cells to reenter the mitotic cell cycle. The use of a yeast mutant that is conditionally blocked in the resumption of proliferation at a step that is not part of the mitotic cell cycle (M.A. Drebot, G.C. Johnston, and R.A. Singer, Proc. Natl. Acad. Sci. 84:7948, 1987) showed that this increased gene expression that occurs upon stimulation of stationary-phase cells took place in the absence of DNA synthesis and without the performance of start. This stimulation-specific gene expression was blocked by the mating pheromone alpha-factor, indicating that alpha-factor directly inhibits expression of these histone genes, independently of start.

scholarly journals Temporal Changes in Gene Expression Profile during Mature Adipocyte Dedifferentiation

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Julie Anne Côté ◽  
Frédéric Guénard ◽  
Julie Lessard ◽  
Marc Lapointe ◽  
Simon Biron ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Cellular Proliferation ◽  
Matrix Remodeling ◽  
Mature Adipocyte ◽  
Tissue Samples ◽  
Ceiling Culture ◽  
Isolated Adipocytes

Objective. To characterize changes in gene expression profile during human mature adipocyte dedifferentiation in ceiling culture.Methods. Subcutaneous (SC) and omental (OM) adipose tissue samples were obtained from 4 participants paired for age and BMI. Isolated adipocytes were dedifferentiated in ceiling culture. Gene expression analysis at days 0, 4, 7, and 12 of the cultures was performed using Affymetrix Human Gene 2.0 STvi arrays. Hierarchical clustering according to similarity of expression changes was used to identify overrepresented functions.Results. Four clusters gathered genes with similar expression between day 4 to day 7 but decreasing expression from day 7 to day 12. Most of these genes coded for proteins involved in adipocyte functions (LIPE,PLIN1,DGAT2,PNPLA2,ADIPOQ,CEBPA,LPL,FABP4,SCD,INSR, andLEP). Expression of several genes coding for proteins implicated in cellular proliferation and growth or cell cycle increased significantly from day 7 to day 12 (WNT5A,KITLG, andFGF5). Genes coding for extracellular matrix proteins were differentially expressed between days 0, 4, 7, and 12 (COL1A1,COL1A2, andCOL6A3,MMP1, andTGFB1).Conclusion. Dedifferentiation is associated with downregulation of transcripts encoding proteins involved in mature adipocyte functions and upregulation of genes involved in matrix remodeling, cellular development, and cell cycle.

Alteration of gene expression profile in mouse embryonic stem cells and neural differentiation deficits by ethephon

2020 ◽  
Vol 39 (11) ◽  
pp. 1518-1527
Author(s):  
S Mohammadi Nejad ◽  
M Hodjat ◽  
SA Mousavi ◽  
M Baeeri ◽  
MA Rezvanfar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Neural Differentiation ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Differentiation Potential

Ethephon, a member of the organophosphorus compounds, is one of the most widely used plant growth regulators for artificial ripening. Although million pounds of this chemical is being used annually, the knowledge regarding its molecular toxicity is yet not sufficient. The purpose of this study was to evaluate the potential developmental toxicity of ethephon using embryonic stem cell model. The mouse embryonic stem cells (mESCs) were exposed to various concentrations of ethephon and the viability, cell cycle alteration and changes in the gene expression profile were evaluated using high-throughput RNA sequencing. Further, the effect of ethephon on neural differentiation potential was examined. The results showed that ethephon at noncytotoxic doses induced cell cycle arrest in mESCs. Gene ontology enrichment analysis showed that terms related to cell fate and organismal development, including neuron fate commitment, embryo development and cardiac cell differentiation, were markedly enriched in ethephon-treated cells. Neural induction of mESCs in the presence of ethephon was inhibited and the expression of neural genes was decreased in differentiated cells. Results obtained from this work clearly demonstrate that ethephon affects the gene expression profile of undifferentiated mESCs and prevents neural differentiation. Therefore, more caution against the frequent application of ethephon is advised.

scholarly journals Gene Expression Profile of Human Mesenchymal Stromal Cells Exposed to Hypoxic and Pseudohypoxic Preconditioning—An Analysis by RNA Sequencing

2021 ◽  
Vol 22 (15) ◽  
pp. 8160
Author(s):  
Katarzyna Zielniok ◽  
Anna Burdzinska ◽  
Victor Murcia Pienkowski ◽  
Agnieszka Koppolu ◽  
Malgorzata Rydzanicz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Sequencing ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Therapeutic Potential ◽  
Phospholipid Metabolism ◽  
Functional Enrichment ◽  
Valuable Insight ◽  
Illumina Platform ◽  
Insight Into

Mesenchymal stromal cell (MSC) therapy is making its way into clinical practice, accompanied by research into strategies improving their therapeutic potential. Preconditioning MSCs with hypoxia-inducible factors-α (HIFα) stabilizers is an alternative to hypoxic priming, but there remains insufficient data evaluating its transcriptomic effect. Herein, we determined the gene expression profile of 6 human bone marrow-derived MSCs preconditioned for 6 h in 2% O2 (hypoxia) or with 40 μM Vadadustat, compared to control cells and each other. RNA-Sequencing was performed using the Illumina platform, quality control with FastQC and adapter-trimming with BBDUK2. Transcripts were mapped to the Homo_sapiens. GRCh37 genome and converted to relative expression using Salmon. Differentially expressed genes (DEGs) were generated using DESeq2 while functional enrichment was performed in GSEA and g:Profiler. Comparison of hypoxia versus control resulted in 250 DEGs, Vadadustat versus control 1071, and Vadadustat versus hypoxia 1770. The terms enriched in both phenotypes referred mainly to metabolism, in Vadadustat additionally to vesicular transport, chromatin modifications and interaction with extracellular matrix. Compared with hypoxia, Vadadustat upregulated autophagic, phospholipid metabolism, and TLR cascade genes, downregulated those of cytoskeleton and GG-NER pathway and regulated 74 secretory factor genes. Our results provide valuable insight into the transcriptomic effects of these two methods of MSCs preconditioning.

scholarly journals Identification of metastasis and prognosis-associated genes for serous ovarian cancer

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Yijun Yang ◽  
Suwan Qi ◽  
Can shi ◽  
Xiao Han ◽  
Juanpeng Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Signaling Pathway ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Tumor Metastasis ◽  
Cox Regression ◽  
Serous Ovarian Cancer ◽  
Hub Genes ◽  
Blue Module

Abstract Serous ovarian cancer is one of the most fatal gynecological tumors with an extremely low 5-year survival rate. Most patients are diagnosed at an advanced stage with wide metastasis. The dysregulation of genes serves an important role in the metastasis progression of ovarian cancer. Differentially expressed genes (DEGs) between primary tumors and metastases of serous ovarian cancer were screened out in the gene expression profile of GSE73168 from Gene Expression Omnibus (GEO). Cytoscape plugin cytoHubba and weighted gene co-expression network analysis (WGCNA) were utilized to select hub genes. Univariate and multivariate Cox regression analyses were used to screen out prognosis-associated genes. Furthermore, the Oncomine validation, prognostic analysis, methylation mechanism, gene set enrichment analysis (GSEA), TIMER database analysis and administration of candidate molecular drugs were conducted for hub genes. Nine hundred and fifty-seven DEGs were identified in the gene expression profile of GSE73168. After using Cytoscape plugin cytoHubba, 83 genes were verified. In co-expression network, the blue module was most closely related to tumor metastasis. Furthermore, the genes in Cytoscape were analyzed, showing that the blue module and screened 17 genes were closely associated with tumor metastasis. Univariate and multivariate Cox regression revealed that the age, stage and STMN2 were independent prognostic factors. The Cancer Genome Atlas (TCGA) suggested that the up-regulated expression of STMN2 was related to poor prognosis of ovarian cancer. Thus, STMN2 was considered as a new key gene after expression validation, survival analysis and TIMER database validation. GSEA confirmed that STMN2 was probably involved in ECM receptor interaction, focal adhesion, TGF beta signaling pathway and MAPK signaling pathway. Furthermore, three candidate small molecule drugs for tumor metastasis (diprophylline, valinomycin and anisomycin) were screened out. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot showed that STMN2 was highly expressed in ovarian cancer tissue and ovarian cancer cell lines. Further studies are needed to investigate these prognosis-associated genes for new therapy target.

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