Browsing by Author "Tian, Fei"
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Item GENOME-WIDE ANALYSIS OF CHICKEN MIRNAS AND DNA METHYLATION AND THEIR ROLES IN MAREK'S DISEASE RESISTANCE AND SUSCEPTIBILITY(2012) Tian, Fei; Song, Jiuzhou; Animal Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Marek's disease (MD) is a T cell lymphoma in chickens and causes high mortality and morbidity in productive chickens. Two inbred chicken lines, resistant line 63 and susceptible line 72, with the same MHC haplotype, showed distinct disease outcomes after MDV infection. The current studies aimed to illustrate the role of microRNA (miRNAs) and DNA methylation in MD resistance and susceptibility in chickens. First, to ascertain the function of miRNAs, miRNA microarray experiments were used to identify miRNAs sensitive to MDV infection in the 2 lines. Most miRNAs were repressed in line 72 after MDV infection, while their transcription was steady in line 63. The miRNA target genes were identified in chickens. Cellular miRNA gga-miR-15b and gga-let-7iwere reduced in infected line 72 chickens and MD tumors. The downregulation of the two miRNAs increased the expression of ATF2 (activating transcription factor 2) and DNMT3a (DNA methyltransferase 3a) in infected line 72. These results indicated that miRNAs may play antiviral functions through modulating target gene expression. Next, to characterize the role of miRNAs in MDV infection, the selected chicken miRNAs were overexpressed in MDV infected DF-1 cells. The overexpressions of chicken miRNA gga-miR-15b and gga-let-7i, by using the retroviral based vector, significantly restricted MDV replications in vitro. MDV oncoprotein was repressed, suggesting that chicken miRNAs may limit MDV propagation. Finally, we found deregulation of transcription of DNA methyltransfereases (DNMTs) in lines 63 and 72 after MDV infection, which coordinated with the methylation alterations in the 2 lines. Infection induced differential methylation regions (iDMRs) that were identified through genome-wide DNA methylation quantification. Genes overlapping line-specific iDMRs were related with pathways of different functions in these two lines, implying the involvement of DNA methylation in MD- resistance and susceptibility. An in vitro study showed that DNA methylation inhibitor repressed viral spread and viral replication. In conclusion, the observed variations of miRNA expression and DNA methylation may be associated with disease predisposition in chickens.Item miRNA-dysregulation associated with tenderness variation induced by acute stress in Angus cattle(Springer Nature, 2012-06-01) Zhao, Chunping; Tian, Fei; Yu, Ying; Liu, George; Zan, Linsen; Updike, M Scott; Song, JiuzhoumiRNAs are a class of small, single-stranded, non-coding RNAs that perform post-transcriptional repression of target genes by binding to 3’ untranslated regions. Research has found that miRNAs involved in the regulation of many metabolic processes. Here we uncovered that the beef quality of Angus cattle sharply diversified after acute stress. By performing miRNA microarray analysis, 13 miRNAs were significantly differentially expressed in stressed group compared to control group. Using a bioinformatics method, 135 protein-coding genes were predicted as the targets of significant differentially expressed miRNAs. Gene Ontology (GO) term and Ingenuity Pathway Analysis (IPA) mined that these target genes involved in some important pathways, which may have impact on meat quality and beef tenderness.Item Temporal transcriptome changes induced by MDV in marek's disease-resistant and -susceptible inbred chickens(Springer Nature, 2011-10-12) Yu, Ying; Luo, Juan; Mitra, Apratim; Chang, Shuang; Tian, Fei; Zhang, Huanmin; Yuan, Ping; Zhou, Huaijun; Song, JiuzhouMarek's disease (MD) is a lymphoproliferative disease in chickens caused by Marek's disease virus (MDV) and characterized by T cell lymphoma and infiltration of lymphoid cells into various organs such as liver, spleen, peripheral nerves and muscle. Resistance to MD and disease risk have long been thought to be influenced both by genetic and environmental factors, the combination of which contributes to the observed outcome in an individual. We hypothesize that after MDV infection, genes related to MD-resistance or -susceptibility may exhibit different trends in transcriptional activity in chicken lines having a varying degree of resistance to MD. In order to study the mechanisms of resistance and susceptibility to MD, we performed genome-wide temporal expression analysis in spleen tissues from MD-resistant line 63, susceptible line 72 and recombinant congenic strain M (RCS-M) that has a phenotype intermediate between lines 63 and 72 after MDV infection. Three time points of the MDV life cycle in chicken were selected for study: 5 days post infection (dpi), 10dpi and 21dpi, representing the early cytolytic, latent and late cytolytic stages, respectively. We observed similar gene expression profiles at the three time points in line 63 and RCS-M chickens that are both different from line 72. Pathway analysis using Ingenuity Pathway Analysis (IPA) showed that MDV can broadly influence the chickens irrespective of whether they are resistant or susceptible to MD. However, some pathways like cardiac arrhythmia and cardiovascular disease were found to be affected only in line 72; while some networks related to cell-mediated immune response and antigen presentation were enriched only in line 63 and RCS-M. We identified 78 and 30 candidate genes associated with MD resistance, at 10 and 21dpi respectively, by considering genes having the same trend of expression change after MDV infection in lines 63 and RCS-M. On the other hand, by considering genes with the same trend of expression change after MDV infection in lines 72 and RCS-M, we identified 78 and 43 genes at 10 and 21dpi, respectively, which may be associated with MD-susceptibility. By testing temporal transcriptome changes using three representative chicken lines with different resistance to MD, we identified 108 candidate genes for MD-resistance and 121 candidate genes for MD-susceptibility over the three time points. Genes included in our resistance or susceptibility genes lists that are also involved in more than 5 biofunctions, such as CD8α, IL8, USP18, and CTLA4, are considered to be important genes involved in MD-resistance or -susceptibility. We were also able to identify several biofunctions related with immune response that we believe play an important role in MD-resistance.