scholarly journals Transcriptional Profiling of Whisker Follicles and of the Striatum in Methamphetamine Self-Administered Rats

2020 ◽  
Vol 21 (22) ◽  
pp. 8856
Author(s):  
Won-Jun Jang ◽  
Taekwon Son ◽  
Sang-Hoon Song ◽  
In Soo Ryu ◽  
Sooyeun Lee ◽  
...  

Methamphetamine (MA) use disorder is a chronic neuropsychiatric disease characterized by recurrent binge episodes, intervals of abstinence, and relapses to MA use. Therefore, identification of the key genes and pathways involved is important for improving the diagnosis and treatment of this disorder. In this study, high-throughput RNA sequencing was performed to find the key genes and examine the comparability of gene expression between whisker follicles and the striatum of rats following MA self-administration. A total of 253 and 87 differentially expressed genes (DEGs) were identified in whisker follicles and the striatum, respectively. Multivariate and network analyses were performed on these DEGs to find hub genes and key pathways within the constructed network. A total of 129 and 49 genes were finally selected from the DEG sets of whisker follicles and of the striatum. Statistically significant DEGs were found to belong to the classes of genes involved in nicotine addiction, cocaine addiction, and amphetamine addiction in the striatum as well as in Parkinson’s, Huntington’s, and Alzheimer’s diseases in whisker follicles. Of note, several genes and pathways including retrograde endocannabinoid signaling and the synaptic vesicle cycle pathway were common between the two tissues. Therefore, this study provides the first data on gene expression levels in whisker follicles and in the striatum in relation to MA reward and thereby may accelerate the research on the whisker follicle as an alternative source of biomarkers for the diagnosis of MA use disorder.

2020 ◽  
Vol 21 (18) ◽  
pp. 6694
Author(s):  
Francesca Capone ◽  
Andrea Polo ◽  
Angela Sorice ◽  
Alfredo Budillon ◽  
Susan Costantini

Selenoproteins are proteins that contain selenium within selenocysteine residues. To date, twenty-five mammalian selenoproteins have been identified; however, the functions of nearly half of these selenoproteins are unknown. Although alterations in selenoprotein expression and function have been suggested to play a role in cancer development and progression, few detailed studies have been carried out in this field. Network analyses and data mining of publicly available datasets on gene expression levels in different cancers, and the correlations with patient outcome, represent important tools to study the correlation between selenoproteins and other proteins present in the human interactome, and to determine whether altered selenoprotein expression is cancer type-specific, and/or correlated with cancer patient prognosis. Therefore, in the present study, we used bioinformatics approaches to (i) build up the network of interactions between twenty-five selenoproteins and identify the most inter-correlated proteins/genes, which are named HUB nodes; and (ii) analyze the correlation between selenoprotein gene expression and patient outcome in ten solid tumors. Then, considering the need to confirm by experimental approaches the correlations suggested by the bioinformatics analyses, we decided to evaluate the gene expression levels of the twenty-five selenoproteins and six HUB nodes in androgen receptor-positive (22RV1 and LNCaP) and androgen receptor–negative (DU145 and PC3) cell lines, compared to human nontransformed, and differentiated, prostate epithelial cells (EPN) by RT-qPCR analysis. This analysis confirmed that the combined evaluation of some selenoproteins and HUB nodes could have prognostic value and may improve patient outcome predictions.


Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 798 ◽  
Author(s):  
Chew ◽  
Petretto

Microglia, the main immune cells of the central nervous system, are increasingly implicated in Alzheimer’s disease (AD). Manifold transcriptomic studies in the brain have not only highlighted microglia’s role in AD pathogenesis, but also mapped crucial pathological processes and identified new therapeutic targets. An important component of many of these transcriptomic studies is the investigation of gene expression networks in AD brain, which has provided important new insights into how coordinated gene regulatory programs in microglia (and other cell types) underlie AD pathogenesis. Given the rapid technological advancements in transcriptional profiling, spanning from microarrays to single-cell RNA sequencing (scRNA-seq), tools used for mapping gene expression networks have evolved to keep pace with the unique features of each transcriptomic platform. In this article, we review the trajectory of transcriptomic network analyses in AD from brain to microglia, highlighting the corresponding methodological developments. Lastly, we discuss examples of how transcriptional network analysis provides new insights into AD mechanisms and pathogenesis.


2021 ◽  
Author(s):  
Ling Zhu ◽  
Xiaoling Ni ◽  
Shanshan Tang ◽  
Wenhua Liu

Abstract Background: The causes of the recurrence of pelvic organ prolapse (POP) are sufficiently understood. However, few studies investigate the key genes of recurrence POP. The present study aimed to screen the hub genes of recurrence POP. Microarray data of 4 recurrent POP and 4 primary POP uterosacral ligaments in the GSE28660 gene expression dataset were used as research objects. we used the online Gene Expression Omnibus (GEO) microarray expression profiling dataset to identify differentially expressed genes (DEGs). Also, functional enrichment and protein-protein interaction (PPI) network analyses were performed, and the key modules were identified. Then, we investigated the differential immune cell infiltration between recurrent POP and primary POP tissues using the CIBERSORT algorithm.Results: In total, 84 upregulated and 32 downregulated genes were identified in the differential expression analysis.Conclusion: This human genome DNA microarrays analysis identified a recurrence POP signature of 116 genes, and 2 hub genes, including cell death-inducing DFFA-like effector (CIDEA) and hemoglobin subunit delta (HBD) may participate in the pathogenesis of recurrence POP, giving them a certain diagnostic and therapeutic value.


2013 ◽  
Vol 12 ◽  
pp. CIN.S11831 ◽  
Author(s):  
Chindo Hicks ◽  
Lucio Miele ◽  
Tejaswi Koganti ◽  
LaFarra Young-Gaylor ◽  
Deidre Rogers ◽  
...  

B-Precursor acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer. Although 80% of B-ALL patients are able to be cured, significant challenges persist. Significant disparities in clinical outcomes and mortality rates exist between racial/ ethnic populations. The objective of this study was to determine whether gene expression levels significantly differ between ethnic populations. We compared gene expression levels between four ethnic populations (Whites, Blacks, Hispanics, and Asians) in the United States. Additionally, we performed network and pathway analysis to identify gene networks and pathways. Gene expression data involved 198 samples distributed as follows: 126 Whites, 51 Hispanics, 13 Blacks, and 8 Asians. We identified 300 highly significantly ( P < 0.001) differentially expressed genes between the four ethnic populations. Among the identified genes included the genes PHF6, BRD3, CRLF2, and RNF135 which have been implicated in pediatric B-ALL. We identified key pathways implicated in B-ALL including the PDGF, PI3/AKT, ERBB2-ERBB3, and IL-15 signaling pathways.


2020 ◽  
Author(s):  
Wenyong Fei ◽  
Mingsheng Liu ◽  
Yao Zhang ◽  
Shichao Cao ◽  
Xuanqi Wang ◽  
...  

Abstract Background: The regeneration of muscle cells from stem cells is an intricate process and various genes are included in the process as myoD, mf5, mf6 etc. The key genes and pathways in the differentiating stages is various. Therefore, the differential expression of key genes after 4weeks of differentiation were investigated in our study. Method: Three published gene expression profiles, GSE131125, GSE148994, GSE149055, about the comparisons of pluripotent stem cells to differentiated cells after 4 weeks were obtained from the Gene Expression Omnibus (GEO) database. Common differentially expressed genes (DEGs) were obtained for further analysis as proteinprotein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and GSEA analysis. After hub genes and key pathways were obtained, we manipulated in vitro cell research for substantiation as immunohistochemical staining and semi-quantitative analysis and quantitative real-time PCR. Results: A total of 824 DEGs including 350 up-regulated genes and 474 down-regulated genes were identified in the three GSEs. 19 hub genes were identified from the PPI network. The GO and KEGG pathway analysis confirmed that myogenic differentiation at 4 weeks was strongly associated with pathway in cancer, PI3K pathway, actin cytoskeleton regulation and metabolic pathway, biosynthesis of antibodies and cell cycle. GSEA analysis indicated the differentiated cells were enriched in muscle cell development and myogenesis. Meanwhile, the core genes in each pathway were identified from the GSEA analysis. The in vitro cell research revealed that actin cytoskeleton and myoD were up-regulated after 4 weeks differentiation. Conclusions: The research revealed the potential hub genes and key pathways after 4 weeks differentiation of stem cells which contribute to further study about the molecular mechanism of myogenesis regeneration. Paving a way for more accurate treatment for muscle dysfunction.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Wenyong Fei ◽  
Mingsheng Liu ◽  
Yao Zhang ◽  
Shichao Cao ◽  
Xuanqi Wang ◽  
...  

Abstract Background The regeneration of muscle cells from stem cells is an intricate process, and various genes are included in the process such as myoD, mf5, mf6, etc. The key genes and pathways in the differentiating stages are various. Therefore, the differential expression of key genes after 4 weeks of differentiation were investigated in our study. Method Three published gene expression profiles, GSE131125, GSE148994, and GSE149055, about the comparisons of pluripotent stem cells to differentiated cells after 4 weeks were obtained from the Gene Expression Omnibus (GEO) database. Common differentially expressed genes (DEGs) were obtained for further analysis such as protein-protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA analysis. After hub genes and key pathways were obtained, we manipulated in vitro cell research for substantiation such as immunohistochemical staining and semi-quantitative analysis and quantitative real-time PCR. Results A total of 824 DEGs including 350 upregulated genes and 474 downregulated genes were identified in the three GSEs. Nineteen hub genes were identified from the PPI network. The GO and KEGG pathway analyses confirmed that myogenic differentiation at 4 weeks was strongly associated with pathway in cancer, PI3K pathway, actin cytoskeleton regulation and metabolic pathway, biosynthesis of antibodies, and cell cycle. GSEA analysis indicated the differentiated cells were enriched in muscle cell development and myogenesis. Meanwhile, the core genes in each pathway were identified from the GSEA analysis. The in vitro cell research revealed that actin cytoskeleton and myoD were upregulated after 4-week differentiation. Conclusions The research revealed the potential hub genes and key pathways after 4-week differentiation of stem cells which contribute to further study about the molecular mechanism of myogenesis regeneration, paving a way for more accurate treatment for muscle dysfunction.


Author(s):  
М.Е. Лопаткина ◽  
В.С. Фишман ◽  
М.М. Гридина ◽  
Н.А. Скрябин ◽  
Т.В. Никитина ◽  
...  

Проведен анализ генной экспрессии в нейронах, дифференцированных из индуцированных плюрипотентных стволовых клеток пациентов с идиопатическими интеллектуальными нарушениями и реципрокными хромосомными мутациями в регионе 3p26.3, затрагивающими единственный ген CNTN6. Для нейронов с различным типом хромосомных аберраций была показана глобальная дисрегуляция генной экспрессии. В нейронах с вариациями числа копий гена CNTN6 была снижена экспрессия генов, продукты которых вовлечены в процессы развития центральной нервной системы. The gene expression analysis of iPSC-derived neurons, obtained from patients with idiopathic intellectual disability and reciprocal microdeletion and microduplication in 3p26.3 region affecting the single CNTN6 gene was performed. The global gene expression dysregulation was demonstrated for cells with CNTN6 copy number variation. Gene expression in neurons with CNTN6 copy number changes was downregulated for genes, whose products are involved in the central nervous system development.


2018 ◽  
Author(s):  
Yihui Chen ◽  
Yaping Jiang ◽  
Xiaoyan Zhang ◽  
Qingzhong Wang

2021 ◽  
Author(s):  
Pavel V. Mazin ◽  
Philipp Khaitovich ◽  
Margarida Cardoso-Moreira ◽  
Henrik Kaessmann

AbstractAlternative splicing (AS) is pervasive in mammalian genomes, yet cross-species comparisons have been largely restricted to adult tissues and the functionality of most AS events remains unclear. We assessed AS patterns across pre- and postnatal development of seven organs in six mammals and a bird. Our analyses revealed that developmentally dynamic AS events, which are especially prevalent in the brain, are substantially more conserved than nondynamic ones. Cassette exons with increasing inclusion frequencies during development show the strongest signals of conserved and regulated AS. Newly emerged cassette exons are typically incorporated late in testis development, but those retained during evolution are predominantly brain specific. Our work suggests that an intricate interplay of programs controlling gene expression levels and AS is fundamental to organ development, especially for the brain and heart. In these regulatory networks, AS affords substantial functional diversification of genes through the generation of tissue- and time-specific isoforms from broadly expressed genes.


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