scholarly journals Characteristics of SP600125 Induced Tetraploid Cells in Comparison With Diploid and Tetraploid Cells of Fish

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunpeng Fan ◽  
Guangjing Zhang ◽  
Kaiyue Zhao ◽  
Wen Fu ◽  
Shujuan Chen ◽  
...  
Keyword(s):  
Crucian Carp ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Mtdna Copy Number ◽  
Chromosome Behavior ◽  
Migration Ability ◽  
Giant Mitochondria ◽  
Ploidy Levels ◽  
Significant Difference ◽  
Cycle Regulation

In our previous research, SP600125 (Anthrapyrazolone) was used to induce autotetraploid of crucian carp cells (SP4N cells), and tetraploid fry was generated from the SP4N cells by somatic cell nuclear transfer technique. However, it is still unclear about biological characteristics of the SP4N cells. In this article, the cytological characteristic and gene expression profiles of the SP4N cells are investigated in comparison with the crucian carp cells (2N cells) and the tetraploid crucian carp cells (CC4N cells). The SP4N cells have tetraploid characteristics in terms of morphology and DNA ploidy levels, and their chromosome behavior is stable during the cell proliferation. The migration ability and the mtDNA copy number of SP4N cells are both lower than those in the CC4N cells and the 2N cells, but there exist giant mitochondria in the SP4N cells. The similar expression trends in the cell cycle regulation genes of the SP4N cells and 2N cells, while the corresponding expression profiles are clearly different between the SP4N cells and the CC4N cells. Moreover, the significant difference genes are associated with energy metabolism pathways among the SP4N cells, 2N cells and CC4N cells. These results can provide deeper understanding of SP600125 induction, as well as finding applications in polyploidization breeding of fish species.

scholarly journals Gender-specific differences in gene expression profiles in gynogenetic Pengze crucian carp

2016 ◽  
Vol 66 (2) ◽  
pp. 157-171
Author(s):  
Yao Zheng ◽  
Jiazhang Chen ◽  
Xuwen Bing ◽  
Yanping Yang ◽  
Hongwei Liang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Crucian Carp ◽  
Expression Profiles ◽  
Gonadosomatic Index ◽  
Gene Expression Profiles ◽  
High Ratio ◽  
Hepatosomatic Index ◽  
Significant Difference ◽  
Gender Specific Differences ◽  
Gender Specific

Gynogenesis is a form of asexual reproduction that is used to obtain all-female fish stocks. In this study, we were interested in studying gender-specific differences in gene expression profiles in gynogenetic teleosts, using a carp species. The four-month old gynogenetic Pengze crucian carp F1 (Carassius auratus var. pengzensis, Pcc) showed a high ratio of males under laboratory culture condition. The present study aimed to investigate the differences between males and females. The gonadosomatic index of the females was significantly higher than that of the males. Moreover, the hepatosomatic index of the females was significantly lower than that of the males. Vitellogenin B mRNA was abnormally highly expressed in male hepatopancreas and testes compared to females. Similarly, zona pellucida 2 expressed at a significantly high level in the testes. For the sex related genes, dosage-sensitive sex reversal, adrenal hypoplasia congenital critical region on the X-chromosome gene 1, doublesex and mab-3 related transcription factor 1a, nuclear receptor subfamily 5, group A, member 1b and SRY-box containing gene 9a had significantly higher expression levels in the males than in the females, whereas there was no difference in expression of anti-Müllerian hormone, cytochrome P450 family 19 subfamily A member 1A and forkhead box L2 transcripts between the two genders. The females showed higher levels of estrogen but no significant difference in testosterone compared to the males. The data suggest remarkable differences between the two genders of the Pengze crucian carp.

scholarly journals Combinatorial targeting of MTHFD2 and PAICS in purine synthesis as a novel therapeutic strategy

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Chantal Hoi Yin Cheung ◽  
Chia-Lang Hsu ◽  
Chao-Yin Tsuei ◽  
Tzu-Ting Kuo ◽  
Chen-Tsung Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Expression Profiles ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Gene Expression Profiles ◽  
Migration Ability ◽  
Purine Synthesis ◽  
One Carbon Metabolism

Abstract MYCN-amplified (MNA) neuroblastoma is an aggressive neural crest-derived pediatric cancer. However, MYCN is indispensable for development and transcriptionally regulates extensive network of genes. Integrating anti-MYCN ChIP-seq and gene expression profiles of neuroblastoma patients revealed the metabolic enzymes, MTHFD2 and PAICS, required for one-carbon metabolism and purine biosynthesis were concomitantly upregulated, which were more susceptible to metastatic neuroblastoma. Moreover, we found that MYCN mediated the folate cycle via MTHFD2, which contributed one-carbon unit to enhance purine synthesis, and further regulated nucleotide production by PAICS in response to cancer progression. Dual knockdown of the MYCN-targeted gene pair, MTHFD2 and PAICS, in MNA neuroblastoma cells synergically reduced cell proliferation, colony formation, migration ability, and DNA synthesis. By systematically screening the compound perturbagens, the gene expression levels of MTHFD2 and PAICS were specifically suppressed by anisomycin and apicidin across cell lines, and our co-treatment results also displayed synergistic inhibition of MNA neuroblastoma cell proliferation. Collectively, targeting a combination of MYCN-targeted genes that interrupts the interconnection of metabolic pathways may overcome drug toxicity and improve the efficacy of current therapeutic agents in MNA neuroblastoma.

scholarly journals Transit-Amplifying Cells in the Fast Lane from Stem Cells towards Differentiation

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Emma Rangel-Huerta ◽  
Ernesto Maldonado
Keyword(s):  
Stem Cells ◽  
Mammalian Cells ◽  
Progenitor Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Differentiated Cells ◽  
Dividing Cells ◽  
Cycle Regulation ◽  
Potential Use ◽  
Skin Epidermis

Stem cells have a high potential to impact regenerative medicine. However, stem cells in adult tissues often proliferate at very slow rates. During development, stem cells may change first to a pluripotent and highly proliferative state, known as transit-amplifying cells. Recent advances in the identification and isolation of these undifferentiated and fast-dividing cells could bring new alternatives for cell-based transplants. The skin epidermis has been the target of necessary research about transit-amplifying cells; this work has mainly been performed in mammalian cells, but further work is being pursued in other vertebrate models, such as zebrafish. In this review, we present some insights about the molecular repertoire regulating the transition from stem cells to transit-amplifying cells or playing a role in the transitioning to fully differentiated cells, including gene expression profiles, cell cycle regulation, and cellular asymmetrical events. We also discuss the potential use of this knowledge in effective progenitor cell-based transplants in the treatment of skin injuries and chronic disease.

scholarly journals Progesterone depletion results in Lamin B1 loss and induction of cell death in mouse trophoblast giant cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254674
Author(s):  
Hiromu Morimoto ◽  
Misuzu Ueno ◽  
Hideyuki Tanabe ◽  
Tomohiro Kono ◽  
Hidehiko Ogawa
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Nuclear Lamina ◽  
Giant Cells ◽  
Specific Gene ◽  
Ploidy Levels ◽  
Lamin B1 ◽  
Trophoblast Giant Cells

Trophoblast giant cells (TGCs), a mouse trophoblast subtype, have large amounts of cytoplasm and high ploidy levels via endocycles. The diverse functions and gene expression profiles of TGCs have been studied well, but their nuclear structures remain unknown. In this study, we focus on Lamin B1, a nuclear lamina, and clarify its expression dynamics, regulation and roles in TGC functions. TGCs that differentiated from trophoblast stem cells were used. From days 0 to 9 after differentiation, the number of TGCs gradually increased, but the amount of LMNB1 peaked at day 3 and then slightly decreased. An immunostaining experiment showed that LMNB1-depleted TGCs increased after day 6 of differentiation. These LMNB1-depleted TGCs diffused peripheral localization of the heterochromatin marker H3K9me2 in the nuclei. However, LMINB1-knock down was not affected TGCs specific gene expression. We found that the death of TGCs also increased after day 6 of differentiation. Moreover, Lamin B1 loss and the cell death in TGCs were protected by 10−6 M progesterone. Our results conclude that progesterone protects against Lamin B1 loss and prolongs the life and function of TGCs.

scholarly journals High expression of RRM2 promotes the pathogenesis of malignant ovarian endometriosis.

2021 ◽  
Author(s):  
Binkai Yang ◽  
Yuanjing Hu ◽  
Tian Wang ◽  
Na Li ◽  
Wenwen Zhang
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Malignant Transformation ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Gene Expression Profiles ◽  
High Expression ◽  
Ovarian Endometriosis ◽  
Ki 67 ◽  
Significant Difference

Abstract Objective: Our objective was to investigate the upregulated expression of ribonucleotide reductase M2 (RRM2) in the ectopic endometrium (EC) of ovarian endometriosis (OE) patients that may indicate malignant transformation. RRM2 may be used as a marker of OE, which contribute to the research of the mechanism of the malignant transformation of OE.Methods: The gene expression profiles of ovarian cancer and OE were downloaded from Gene Expression Omnibus (GEO), and a common hub gene, RRM2, was identified. The expression of RRM2 was low in OE and high in ovarian cancer. A total of 44 patients with endometriosis-associated ovarian cancers (EAOC) and 44 with OE were enrolled in this study. Immunohistochemistry (IHC) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the expression of RRM2, while the relationship between RRM2 and Ki-67 was analyzed by IHC co-localization. Results: There was no significant difference in the expression of RRM2 in the eutopic endometrium (EU), EC, and cancer tissues of EAOC patients. Compared with OE patients, the mRNA and protein expression levels of RRM2 were higher in the EC of EAOC patients (p＜0.01). Moreover, the high expression of RRM2 was consistent with the expression of Ki-67 in EC of EAOC patients.Conclusions: The upregulated expression of RRM2 in the EC of OE patients may indicate malignant transformation. RRM2 may be used as a marker of OE, which allows the investigation of the mechanism of the malignant transformation of OE.

scholarly journals Identification of prognosis-related genes in the cervical cancer immune microenvironment

2020 ◽  
Author(s):  
Lirong Yang ◽  
Yang Yang ◽  
Mingyao Meng ◽  
Wenju Wang ◽  
Shan He ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Tumor Microenvironment ◽  
Clinical Data ◽  
Immune Cells ◽  
Stromal Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Malignant Tumours ◽  
Significant Difference

Abstract Background Cervical cancer is the fourth most common cancer in women worldwide. The metastasis and invasion of this type of cancer are closely related to the tumor microenvironment. Immune cells and stromal cells dominate the tumor microenvironment in cervical cancer. Therefore, we should further understand the association between tumor progress and immune cells or stromal cells.Methods we downloaded the gene expression profiles and clinical data of 307 patients with cervical cancers based on the TCGA database. Subsequently the Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm was used to calculate the scores of stromal cells and immune cells to find differential genes, and analyzed the correlation between their scores and patient survival. Moreover, we also used R language packs and network tools to analyze GO term, gene enrichment pathway, and protein-protein relationship to find genes related to inflammation and immune regulation.Results The gene expression profiles and corresponding clinical data of 307 patients were obtained from TCGA datasets. The results showed that there was a statistically significant difference between the high immunescore group and the low immunescore group. And the low immunescore group had shorter lifetimes than the high scores group (P = 0.035).Moreover, PPI network analysis CCR5 and CXCL9, -10, -11 / CXCR3 axis might be new target for cervical cancer treatment. Finally, Kaplan-Meier survival curves found out nine representative genes significantly related to survival including BTNL8 , CCR7 , CD1E , CD6 , CD27 , CD79A , GRAP2 , SP1B , LY9 .Conclusions These genes can be used as markers for the prognosis and diagnosis of cervical cancer and also might be used as treatment targets.

Activation of intracellular signaling pathways as a new type of biomarkers for selection of target anticancer drugs.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23142-e23142 ◽  
Author(s):  
Anton Buzdin ◽  
Maxim Sorokin ◽  
Alexander Glusker ◽  
Andrew Garazha ◽  
Elena Poddubskaya ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Patients ◽  
Intracellular Signaling ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Molecular Targets ◽  
Signalling Pathways ◽  
Pathway Activation ◽  
Significant Difference ◽  
Selection Of

e23142 Background: Anticancer target drugs (ATDs) specifically bind and inhibit molecular targets that play important roles in tumorigenesis. More than 150 different ATDs have been approved for clinical use worldwide, and the clinicians are faced with the problem of choosing the best therapeutic solution for each patient. The problem of efficient ATD selection remains largely unsolved and personalized approaches are needed to select the best ATD candidates for individual patients. Methods: We propose a new approach termed OncoFinder. It is based on digesting gene expression profiles for the analysis of activation of intracellular signalling pathways as a marker for the selection of target therapies. The original bioinformatic algorithms were integrated with the databases featuring molecular drug targets, compositions of signalling pathways, including the functional role of each gene product, for more than 1700 pathways (Buzdin, Front.Genet 2014; Ozerov, Nature Communications 2016). Results: We showed that pathway activation strengths are more stable and reliable biomarkers of cancer than the expressions of individual genes. OncoFinder allows to detect changes at the level of pathway activation and to predict the effectiveness of drugs based on the knowledge of their molecular targets. We applied it to find new biomarkers of clinical response to the ATD cetuximab; for modelling the combined chemotherapy of acute myeloid leukemia and combined anti-VEGF/BRAF therapy of melanoma. For two unrelated datasets obtained for colon cancer patients before treatment with the ATD bevacizumab, we were able to distinguish between those who responded to treatment and not (p < 0.01). We next assayed biopsies for kidney cancer patients with known responses to the ATD sorafenib. The responders and non-responders showed a significant difference (p = 0.02). Finally, the OncoFinder platform was prospectively used for decision making support to patients with advanced metastatic solid tumors (n = 23). The efficiency of the ATD treatment was 61% (complete + partial response, RECIST). Conclusions: OncoFinder method may be effective for predicting response to ATD based on high throughput gene expression profiles.

scholarly journals Altered metabolic and inflammatory transcriptomics after cardiac surgery in neonates with congenital heart disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Parag N. Jain ◽  
Matthew Robertson ◽  
Javier J. Lasa ◽  
Lara Shekerdemian ◽  
Danielle Guffey ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Whole Blood ◽  
Congenital Heart ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
High Risk Population ◽  
Low Cardiac Output Syndrome ◽  
Significant Difference ◽  
Before And After

AbstractThe study examines the whole blood transcriptome profile before and after cardiopulmonary bypass (CPB) in neonates with hypoplastic left heart syndrome (HLHS), a severe form of congenital heart disease, that can develop low cardiac output syndrome (LCOS). Whole blood mRNA transcriptome profiles of 13 neonates with HLHS before and after their first palliative surgery were analyzed to determine differentially expressed genes and pathways. The median age and weight at surgery were 4 days and 3.2 kg, respectively. Of the 13 patients, 8 developed LCOS. There was no significant difference between CPB, aortic cross clamp, deep hypothermic cardiac arrest times between patients that develop LCOS and those that do not. Upon comparing differential gene expression profiles between patients that develop LCOS and those that do not in pre-operative samples, 1 gene was up-regulated and 13 were down regulated. In the post-operative samples, 4 genes were up-regulated, and 4 genes were down regulated when patients that develop LCOS were compared to those that do not. When comparing post-operative samples to pre-operative samples in the patients that do not develop LCOS, 1484 genes were up-regulated, and 1388 genes were down regulated; while patients that developed LCOS had 2423 up-regulated genes, and 2414 down regulated genes for the same pre to post-operative comparison. Pathway analysis revealed differential regulation of inflammatory pathways (IL signaling, PDGF, NOTCH1, NGF, GPCR) and metabolic pathways (heme metabolism, oxidative phosphorylation, protein metabolism including amino acid and derivatives, fatty acid metabolism, TCA cycle and respiratory electron transport chain). By identifying altered transcriptome profiles related to inflammation and metabolism in neonates with HLHS who develop LCOS after CPB, this study opens for exploration novel pathways and potential therapeutic targets to improve outcomes in this high-risk population.

scholarly journals Integrated Analysis of a Gene Correlation Network Identifies Critical Regulation of Fibrosis by lncRNAs and TFs in Idiopathic Pulmonary Fibrosis

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Fan Wang ◽  
Pei Li ◽  
Feng-sen Li
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Pcr Analysis ◽  
Unknown Etiology ◽  
Integrated Analysis ◽  
Protein Protein Interaction ◽  
Lncrna Malat1 ◽  
Significant Difference

Idiopathic pulmonary fibrosis (IPF), the most frequent form of irreversible interstitial pneumonia with unknown etiology, is characterized by massive remodeling of lung architecture and followed by progressive loss of lung function. However, the key regulatory genes and the specific signaling pathways involved in the onset and progression of IPF still remain unclear. The present study is aimed at investigating the key role of long noncoding RNAs (lncRNAs) and transcription factors (TFs) involved in the pathogenesis of IPF through the integrated analysis of three gene expression profiles from the GEO dataset (GSE2052, GSE44723, and GSE24206). A total of 8483 differentially expressed genes (DEGs) including 988 upregulated and 7495 downregulated genes were filtered. Subsequently, following the intersection of these DEGs, 29 overlapping genes were identified and further analyzed using a bioinformatics approach. Furthermore, the protein-protein interaction (PPI) network was used to obtain 18 modules of related genes. The hub genes were identified through hypergeometric testing, which were closely associated with ubiquitin-mediated proteolysis, the spliceosome, and the cell cycle. The significant difference was observed in the expression of these key genes, such as lncRNA MALAT1, E2F1, and YBX1, in the peripheral blood of IPF patients when compared with those normal control subjects by real-time polymerase chain reaction (RT-PCR) analysis. This study indicated that lncRNA MALAT1, E2F1, and YBX1 may be key regulators for the pathogenesis of IPF.

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