scholarly journals Systems approaches identify the consequences of monosomy in somatic human cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Narendra Kumar Chunduri ◽  
Paul Menges ◽  
Xiaoxiao Zhang ◽  
Angela Wieland ◽  
Vincent Leon Gotsmann ◽  
...  
Keyword(s):  
Ribosome Biogenesis ◽  
Proteome Analysis ◽  
Enrichment Analysis ◽  
Human Cells ◽  
Pathway Enrichment Analysis ◽  
Global Changes ◽  
Chromosome Loss ◽  
P53 Expression ◽  
Expression Of Genes ◽  
P53 Inactivation

AbstractChromosome loss that results in monosomy is detrimental to viability, yet it is frequently observed in cancers. How cancers survive with monosomy is unknown. Using p53-deficient monosomic cell lines, we find that chromosome loss impairs proliferation and genomic stability. Transcriptome and proteome analysis demonstrates reduced expression of genes encoded on the monosomes, which is partially compensated in some cases. Monosomy also induces global changes in gene expression. Pathway enrichment analysis reveals that genes involved in ribosome biogenesis and translation are downregulated in all monosomic cells analyzed. Consistently, monosomies display defects in protein synthesis and ribosome assembly. We further show that monosomies are incompatible with p53 expression, likely due to defects in ribosome biogenesis. Accordingly, impaired ribosome biogenesis and p53 inactivation are associated with monosomy in cancer. Our systematic study of monosomy in human cells explains why monosomy is so detrimental and reveals the importance of p53 for monosomy occurrence in cancer.

scholarly journals Systems approaches identify the consequences of monosomy in somatic human cells

2021 ◽  
Author(s):  
Narendra Kumar Chunduri ◽  
Paul Menges ◽  
Vincent Leon Gotsmann ◽  
Xiaoxiao Zhang ◽  
Balca R. Mardin ◽  
...  
Keyword(s):  
Ribosome Biogenesis ◽  
Gene Dosage ◽  
Genomic Stability ◽  
Proteome Analysis ◽  
Global Gene Expression ◽  
Human Cells ◽  
Chromosome Loss ◽  
G1 Arrest ◽  
P53 Inactivation ◽  
Partial Compensation

AbstractChromosome loss that results in monosomy is detrimental to viability, yet, it is frequently observed in cancers. How cancers survive with monosomy is unknown. Using p53 deficient monosomic cell lines, we found that chromosome loss impairs proliferation and genomic stability. Transcriptome and proteome analysis revealed a partial compensation of the gene dosage changes that mitigates the effects of chromosome loss. Monosomy triggers global gene expression changes that differ from the effects of trisomy. We show that ribosome biogenesis and translation were commonly downregulated in monosomic cells, likely due to haploinsufficiency of ribosomal genes. The ensuing ribosome biogenesis stress triggers the p53 pathway and G1 arrest when TP53 is reintroduced into monosomic cells. Accordingly, impaired ribosome biogenesis and p53 inactivation are associated with monosomy in cancer. Our first systematic study of monosomy in human cells explains why monosomy is so detrimental and how loss of p53 enables its incidence in cancer.

scholarly journals Transcriptomic analysis of Procambarus clarkii affected by “Black May” disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Guoqing Shen ◽  
Xiao Zhang ◽  
Jie Gong ◽  
Yang Wang ◽  
Pengdan Huang ◽  
...  
Keyword(s):  
Procambarus Clarkii ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Apoptosis Pathway ◽  
Pathway Enrichment ◽  
Cellular Processes ◽  
Expression Of Genes ◽  
Muscle Tissues

AbstractEach year from April to May, high mortality rates are reported in red swamp crayfish (Procambarus clarkii) cultured in Jiangsu and other regions, in China, and this phenomenon has come to be known as “Black May” disease (BMD). Therefore, in order to investigate the possible causes of this disease, this study gathered BMD-affected P. clarkii samples and performed transcriptome analysis on hepatopancreas, gill, and muscle tissues. A total of 19,995,164, 149,212,804, and 222,053,848 clean reads were respectively obtained from the gills, muscle, and hepatopancreas of BMD-affected P. clarkii, and 114,024 unigenes were identified. The number of differentially expressed genes (DEGs) in gill, muscle, and hepatopancreas was 1703, 964, and 476, respectively. GO and KEGG enrichment analyses of the DEGs were then conducted. Based on KEGG pathway enrichment analysis, the most significantly differentially expressed pathways were mainly those involved with metabolism, human disease, and cellular processes. Further analysis of the significantly DEGs revealed that they were mainly related to the mitochondrial-mediated apoptosis pathway and that the expression of these DEGs was mostly down-regulated. Moreover, the expression of genes related to immune and metabolism-related pathways was also significantly down-regulated, and these significantly-inhibited pathways were the likely causes of P. clarkii death. Therefore, our results provide a basis for the identification of BMD causes.

scholarly journals Tissue-based metabolomics reveals metabolic signatures and major metabolic pathways of gastric cancer with help of transcriptomic data from TCGA

2021 ◽  
Author(s):  
Ya qin Wang ◽  
Wen chao Chen ◽  
Kun Li ◽  
Gang Wu ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Metabolic Pathways ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Overlapping Genes ◽  
Expression Of Genes ◽  
Human Protein Atlas ◽  
Transcriptomics Data

Purpose: The aim of this study was to screen differential metabolites of gastric cancer (GC) and identify the key metabolic pathways of GC. Methods: GC (n=28) and matched paracancerous (PC) tissues were collected, and LC-MS/MS analysis were performed to detect metabolites of GC and PC tissues. Metabolite pathways based on differential metabolites were enriched by MetaboAnalyst, and genes related to metabolite pathways were identified using the KEGGREST function of the R software package. Transcriptomics data from The Cancer Genome Atlas (TCGA) was analyzed to obtain differentially expressed genes (DEGs) of GC. Overlapping genes were acquired from metabonimics and transcriptomics data. Pathway enrichment analysis was performed using String. The protein expression of genes was validated by the Human Protein Atlas (HPA) database. Results: A total of 325 key metabolites were identified, 111 of which were differentially expressed between the GC and PC groups. Seven metabolite pathways enriched by MetaboAnalyst were chosen, and 361 genes were identified by KEGGREST. A total of 2831 DEGs were identified from the TCGA cohort. Of these, 1317 were down-regulated, and 1636 were up-regulated. Twenty-two overlapping genes were identified between genes related to metabolism and DEGs. Glycerophospholipid (GPL) metabolism is likely associated with GC, of which AGPAT9 and ETNPPL showed lower expressed in GC tissues. Conclusions: We investigated the tissue-based metabolomics profile of GC, and several differential metabolites were identified. GPL metabolism may affect on progression of GC.

scholarly journals Integrated Omics Analyses Identify Key Pathways Involved in Petiole Rigidity Formation in Sacred Lotus

2020 ◽  
Vol 21 (14) ◽  
pp. 5087
Author(s):  
Ming Li ◽  
Ishfaq Hameed ◽  
Dingding Cao ◽  
Dongli He ◽  
Pingfang Yang
Keyword(s):  
Cell Wall ◽  
Lignin Biosynthesis ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Anatomic Structure ◽  
Sacred Lotus ◽  
Expression Of Genes ◽  
The Difference ◽  
Key Pathways

Sacred lotus (Nelumbo nucifera Gaertn.) is a relic aquatic plant with two types of leaves, which have distinct rigidity of petioles. Here we assess the difference from anatomic structure to the expression of genes and proteins in two petioles types, and identify key pathways involved in petiole rigidity formation in sacred lotus. Anatomically, great variation between the petioles of floating and vertical leaves were observed. The number of collenchyma cells and thickness of xylem vessel cell wall was higher in the initial vertical leaves’ petiole (IVP) compared to the initial floating leaves’ petiole (IFP). Among quantified transcripts and proteins, 1021 and 401 transcripts presented 2-fold expression increment (named DEGs, genes differentially expressed between IFP and IVP) in IFP and IVP, 421 and 483 proteins exhibited 1.5-fold expression increment (named DEPs, proteins differentially expressed between IFP and IVP) in IFP and IVP, respectively. Gene function and pathway enrichment analysis displayed that DEGs and DEPs were significantly enriched in cell wall biosynthesis and lignin biosynthesis. In consistent with genes and proteins expressions in lignin biosynthesis, the contents of lignin monomers precursors were significantly different in IFP and IVP. These results enable us to understand lotus petioles rigidity formation better and provide valuable candidate genes information on further investigation.

scholarly journals Peroxisome import stress impairs ribosome biogenesis and induces endoplasmic reticulum genes

2020 ◽  
Author(s):  
Kerui Huang ◽  
Jinoh Kim ◽  
Hua Bai
Keyword(s):  
Endoplasmic Reticulum ◽  
Cellular Response ◽  
Ribosome Biogenesis ◽  
Enrichment Analysis ◽  
Transcriptome Profiling ◽  
Human Cells ◽  
Gene Set Enrichment Analysis ◽  
Cleavage Sites ◽  
Peroxisome Biogenesis ◽  
And Function

AbstractPeroxisome biogenesis diseases (PBDs) are characterized by global defects in peroxisomal function and can result in severe brain, liver, kidney, and bone malfunctions. PBDs are due to mutations in peroxisome biogenesis factors (PEX genes) that are responsible for peroxisome assembly and function. There is increasing evidence suggesting that peroxisome import functions decline during aging. The transcriptome profiling of peroxisome import defects is still lacking. To identify conserved responses, we undertook a bioinformatic transcriptomic analysis on Drosophila oenocyte specific Pex1, Pex12 and Pex5 knockdowns. In addition, we performed analysis on human cells with induced peroxisome import stress. We uncovered that oenocyte-specific Pex1, Pex12 and Pex5 have distinct transcriptional profiles with each other. Using gene set enrichment analysis (GSEA), we identified protein processing in endoplasmic reticulum pathway, specifically ER-associated protein degradation (ERAD) pathway is enriched and induced in all PEX knockdowns in Drosophila. Moreover, we uncovered decreased expression in ribosome biogenesis genes in flies and human cells. Indeed, we identified a stall at the 5’-ETS cleavage sites during the ribosome biogenesis and impaired 40S small ribosomal export in both flies and human. Our data indicates an unexpected link between peroxisome and ribosome biogenesis. Our results suggest that reduced ribosome biogenesis could be conserved cellular response to reduce peroxisome import stress.

scholarly journals Identification of candidate genes and proteins in aging skeletal muscle (sarcopenia) using gene expression and structural analysis

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5239 ◽  
Author(s):  
Gita Shafiee ◽  
Yazdan Asgari ◽  
Akbar Soltani ◽  
Bagher Larijani ◽  
Ramin Heshmat
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Ribosome Biogenesis ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Lipid Storage ◽  
Integrated Analysis ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Men And Women

Sarcopenia is an age-related disease characterized by the loss of muscle mass and muscle function. A proper understanding of its pathogenesis and mechanisms may lead to new strategies for diagnosis and treatment of the disease. This study aims to discover the underlying genes, proteins, and pathways associated with sarcopenia in both genders. Integrated analysis of microarray datasets has been performed to identify differentially expressed genes (DEGs) between old and young skeletal muscles. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were then performed to uncover the functions of the DEGs. Moreover, a protein–protein interaction (PPI) network was constructed based on the DEGs. We have identified 41,715 DEGs, including 19 downregulated and 41,696 upregulated ones, in men. Among women, 3,015 DEGs have been found, with 2,874 of them being upregulated and 141 downregulated genes. Among the top up-regulated and downregulated genes, the ribosome biogenesis genes and genes involved in lipid storage may be closely related to aging muscles in men and women respectively. Also, the DEGs were enriched in the pathways including those of ribosome and Peroxisome proliferator-activated receptor (PPAR) in men and women, respectively. In the PPI network, Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1), Cullin 3 (CUL3) and P53 have been identified as significant hub proteins in both genders. Using the integrated analysis of multiple gene expression profiles, we propose that the ribosome biogenesis genes and those involved in lipid storage would be promising markers for sarcopenia in men and women, respectively. In the reconstructed PPI network, neurotrophic factors expressed in skeletal muscle are essential for motoneuron survival and muscle fiber innervation during development. Cullin E3 ubiquitin ligase (Cul3) is an important component of the ubiquitin–proteasome system—it regulates the proteolysis. P53 is recognized as a central regulator of the cell cycle and apoptosis. These proteins, which have been identified as the most significant hubs, may be involved in aging muscle and sarcopenia.

scholarly journals Platelet proteome analysis reveals an early hyperactive phenotype in SARS-CoV-2-infected humanized ACE2 mice

2021 ◽  
Author(s):  
Saravanan Subramaniam ◽  
Ryan Matthew Hekman ◽  
Archana Jayaraman ◽  
Aoife Kateri O'Connell ◽  
Paige Montanaro ◽  
...  
Keyword(s):  
Severe Disease ◽  
Clinical Signs ◽  
Proteome Analysis ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Valuable Insight ◽  
Platelet Aggregates ◽  
Protein Alterations ◽  
Interferon Responses ◽  
Recognition Receptor

Coronavirus disease-2019 (COVID-19) provokes a hypercoagulable state with increased incidence of thromboembolism and mortality. Platelets are major effectors of thrombosis and hemostasis. Suitable animal models are needed to better understand COVID-19-associated coagulopathy (CAC) and underlying platelet phenotypes. Here, we assessed K18-hACE2 mice undergoing a standardized SARS-CoV-2 infection protocol to study dynamic platelet responses via mass spectrometry-based proteomics. In total, we found significant changes in >1,200 proteins. Strikingly, protein alterations occurred rapidly by 2 days post-infection (dpi) and preceded outward clinical signs of severe disease. Pathway enrichment analysis of 2dpi platelet proteomes revealed that SARS-CoV-2 infection upregulated complement-coagulation networks (F2, F12, CFH, CD55/CD59), platelet activation-adhesion-degranulation proteins (PF4, SELP, PECAM1, HRG, PLG, vWF), and chemokines (CCL8, CXCL5, CXCL12). When mice started to lose weight at 4dpi, pattern recognition receptor signaling (RIG-I/MDA5, CASP8, MAPK3), and interferon pathways (IFIT1/IFIT3, STAT1) were predominant. Interestingly, SARS-CoV-2 spike protein in the lungs was observed by immunohistochemistry, but in platelets was undetected by proteomics. Similar to patients, K18-hACE2 mice during SARS-CoV-2 infection developed progressive lymphohistiocytic interstitial pneumonia with platelet aggregates in the lungs and kidneys. In conclusion, this model recapitulates activation of coagulation, complement, and interferon responses in circulating platelets, providing valuable insight into platelet pathology during COVID-19.

scholarly journals Ionising Radiation Induces Promoter DNA Hypomethylation and Perturbs Transcriptional Activity of Genes Involved in Morphogenesis during Gastrulation in Zebrafish

2020 ◽  
Vol 21 (11) ◽  
pp. 4014
Author(s):  
Sophia Murat El Houdigui ◽  
Christelle Adam-Guillermin ◽  
Olivier Armant
Keyword(s):  
Transcriptional Activity ◽  
Biological Effects ◽  
Enrichment Analysis ◽  
Ionising Radiation ◽  
Mitochondrial Activity ◽  
Pathway Enrichment Analysis ◽  
Dna Hypomethylation ◽  
Dose Rates ◽  
Expression Of Genes ◽  
Promoter Dna

Embryonic development is particularly vulnerable to stress and DNA damage, as mutations can accumulate through cell proliferation in a wide number of cells and organs. However, the biological effects of chronic exposure to ionising radiation (IR) at low and moderate dose rates (< 6 mGy/h) remain largely controversial, raising concerns for environmental protection. The present study focuses on the molecular effects of IR (0.005 to 50 mGy/h) on zebrafish embryos at the gastrula stage (6 hpf), at both the transcriptomics and epigenetics levels. Our results show that exposure to IR modifies the expression of genes involved in mitochondrial activity from 0.5 to 50 mGy/h. In addition, important developmental pathways, namely, the Notch, retinoic acid, BMP and Wnt signalling pathways, were altered at 5 and 50 mGy/h. Transcriptional changes of genes involved in the morphogenesis of the ectoderm and mesoderm were detected at all dose rates, but were prominent from 0.5 to 50 mGy/h. At the epigenetic level, exposure to IR induced a hypomethylation of DNA in the promoter of genes that colocalised with both H3K27me3 and H3Kme4 histone marks and correlated with changes in transcriptional activity. Finally, pathway enrichment analysis demonstrated that the DNA methylation changes occurred in the promoter of important developmental genes, including morphogenesis of the ectoderm and mesoderm. Together, these results show that the transcriptional program regulating morphogenesis in gastrulating embryos was modified at dose rates greater than or equal to 0.5 mGy/h, which might predict potential neurogenesis and somitogenesis defects observed at similar dose rates later in development.

scholarly journals Development and Maturation of the Immune System in Preterm Neonates: Results from a Whole Genome Expression Study

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Magdalena Zasada ◽  
Przemko Kwinta ◽  
Wojciech Durlak ◽  
Mirosław Bik-Multanowski ◽  
Anna Madetko-Talowska ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Gestational Age ◽  
Differential Expression Analysis ◽  
Enrichment Analysis ◽  
Cell Receptor ◽  
Preterm Neonates ◽  
Pathway Enrichment Analysis ◽  
Expression Of Genes ◽  
Immune System Development

To expand the knowledge about the consecutive expression of genes involved in the immune system development in preterm neonates and to verify if the environment changes the gene expression after birth we conducted a prospective study that included three cohorts: (A) extremely (gestational age (GA): 23–26 weeks;n=41), (B) very (GA: 27–29 weeks;n=39), and (C) moderately preterm infants (GA: 30–32 weeks;n=33). Blood samples were drawn from the study participants on the 5th and 28th day of life (DOL). The mRNA samples were evaluated for gene expression with the use of GeneChip Human Gene 1.0ST microarrays. Differential expression analysis revealed small subsets of genes that presented positive or negative monotone trends in both the 5th (138 genes) and 28th DOL (308 genes) in the three subgroups of patients. Based on pathway enrichment analysis, we found that most of the pathways that revealed a positive monotone trend were involved in host immunity. The most significantly GA dependent pathways were T-cell receptor signaling pathway and intestinal immune network for IgA production. Overall 4431 genes were differentially expressed between the 5th and 28th DOL. Despite differences in gestational age, patients with the same postconceptional age have a very similar expression of genes.

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