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 ◽  
...  

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.

2009 ◽  
Vol 37 (1) ◽  
pp. 12-22 ◽  
Author(s):  
Patricia D. Maningat ◽  
Partha Sen ◽  
Monique Rijnkels ◽  
Agneta L. Sunehag ◽  
Darryl L. Hadsell ◽  
...  

The molecular physiology underlying human milk production is largely unknown because of limitations in obtaining tissue samples. Determining gene expression in normal lactating women would be a potential step toward understanding why some women struggle with or fail at breastfeeding their infants. Recently, we demonstrated the utility of RNA obtained from breast milk fat globule (MFG) to detect mammary epithelial cell (MEC)-specific gene expression. We used MFG RNA to determine the gene expression profile of human MEC during lactation. Microarray studies were performed using Human Ref-8 BeadChip arrays (Illumina). MFG RNA was collected every 3 h for 24 h from five healthy, exclusively breastfeeding women. We determined that 14,070 transcripts were expressed and represented the MFG transcriptome. According to GeneSpring GX 9, 156 ontology terms were enriched (corrected P < 0.05), which include cellular ( n = 3,379 genes) and metabolic ( n = 2,656) processes as the most significantly enriched biological process terms. The top networks and pathways were associated primarily with cellular activities most likely involved with milk synthesis. Multiple sampling over 24 h enabled us to demonstrate core circadian clock gene expression and the periodicity of 1,029 genes (7%) enriched for molecular functions involved in cell development, growth, proliferation, and cell morphology. In addition, we found that the MFG transcriptome was comparable to the metabolic gene expression profile described for the lactating mouse mammary gland. This paper is the first to describe the MFG transcriptome in sequential human samples over a 24 h period, providing valuable insights into gene expression in the human MEC.


2020 ◽  
Author(s):  
Jing Luo ◽  
Zhenwei Liu ◽  
Chenlu Li ◽  
Ruochen Wang ◽  
Jinxia Fang ◽  
...  

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.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 289-289 ◽  
Author(s):  
Laurence de Leval ◽  
David Rickman ◽  
Caroline Thielen ◽  
Aurélien de Reynies ◽  
Yen-Lin Huang ◽  
...  

Abstract AITL and PTCL-U, the two most common forms of T-cell lymphomas in western countries, usually present as nodal disease and pursue an aggressive clinical course. AITL is commonly associated with a constellation of clinical symptoms and distinct pathological features. Conversely, PTCL-U lacks precise diagnostic criteria, and by default comprises cases not fulfilling criteria for other entities, including tumors with borderline features to ALCL and AITL. The genetic alterations and pathogenic mechanisms underlying AITL and PTCL-U are largely unknown. To determine whether the molecular signature of AITL and PTCL-U could help in distinguishing both entities and in understanding ther ontogeny, we performed gene expression profile (GEP) analysis of 15 PTCL-U tissue samples (6 CD30+ and 9 CD30−) and 19 AITL samples (including 2 sorted tumor cell suspensions) using Affymetrix HG-U133A Plus2.0 pan-genomic oligonucleotide microarrays, with comparison to that of previously published normal T-cell subsets (J Immunol173:68; J Immunol175: 7837; Blood 104: 1952). Principle component analysis (PCA, accumulated variance 95%) of all 33 tissue samples yielded three groups of tumors: one group of 12 AITLs, one group of 10 PTCLs-U and one mixed group comprising 5 AITLs (some with features borderline to PTCL-U) and 6 PTCLs-U (including 5 of 6 CD30+ tumors). The AITL molecular signature consisted of 442 genes with increased levels of expression in AITL compared to PTCL-U (t test, p<0.002), including genes encoding cell adhesion molecules, immune receptors, extracellular matrix components and several chemokines, B-cell-related and follicular dendritic cell-related genes, genes involved in endothelial and vascular biology, and several genes reported to belong to the gene expression signature of normal TFH cells (CXCL13, BCL6, PDCD1, CD40L, CD200). To specifically address the question of a molecular link beween AITL and TFH cells, we performed gene set enrichment analysis (GSEA) of our dataset using published gene sets specific of distinct normal T-cell subsets (TFH, TH1, TH2). Compared to that of PTCL-U, the molecular signature of AITL was significantly enriched in TFH-specific genes, and the enrichment was even higher for sorted AITL cells compared to AITL tissues. GSEA failed to disclose a molecular link between PTCL-U and known T-cell subsets (TH1, TH2, TFH). Compared to CD30− PTCL-U, CD30+ PTCL-U had lower expression of genes involved in TCR signalling (t test, p<0.002), and showed molecular similarities with ALK-negative ALCL. In conclusion, GEP of non-anaplastic nodal PTCL (1) segregates AITL and PTCL-U, supporting the basis for histotyping; (2) shows molecular analogies between AITL and TFH cells, strongly supporting the hypothesis of a histogenetic link; (3) suggests molecular analogies between CD30+ PTCL-U and ALK-negative ALCL.


2020 ◽  
Vol 39 (11) ◽  
pp. 1518-1527
Author(s):  
S Mohammadi Nejad ◽  
M Hodjat ◽  
SA Mousavi ◽  
M Baeeri ◽  
MA Rezvanfar ◽  
...  

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.


2019 ◽  
Author(s):  
Jing Luo ◽  
Zhenwei Liu ◽  
Chenlu Li ◽  
Ruochen Wang ◽  
Jinxia Fang ◽  
...  

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.


2003 ◽  
Vol 195 (2) ◽  
pp. 221-233 ◽  
Author(s):  
M.Ahmad Chaudhry ◽  
Lewis A. Chodosh ◽  
W.Gillies McKenna ◽  
Ruth J. Muschel

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