Dataset Information

Genome-wide analyses and functional profiling of human NK cell lines.

ABSTRACT: Natural killer (NK) cell lines, including YTS, NK92, NK3.3, and NKL, represent excellent models for the study of human natural killer cells. While phenotypic and functional differences between these cell lines have been reported, a multi-parametric study, encompassing genomic, phenotypic, and functional assays, has not been performed. Here, using a combination of techniques including microarray and copy number analyses, flow cytometry, and functional assays, we provide in-depth genetic, functional, and phenotypic comparison of YTS, NK92, NK3.3, and NKL cell lines. Specifically, we found that while the cell lines shared similarities in enrichment of growth and survival pathways, they had differential expression of 557 genes, including genes related to NK cell development, survival, and function. In addition, we provide genetic and phenotypic analyses that demonstrate distinct developmental origins of NK92, YTS, and NKL cell lines. Specifically, NK92 has a phenotype associated with the CD56bright NK cell subset, while both YTS and NKL appear more CD56dim-like. Finally, by classifying cell lines based on their lytic potential, we identified genes differentially expressed between NK cell lines with high and low lytic function. Taken together, these data provide the first comprehensive genetic, phenotypic, and functional analyses of these commonly used NK cell lines and provides deeper understanding into their origins and function. This will ultimately improve their use as models for human NK cell biology.

SUBMITTER: Gunesch JT

PROVIDER: S-EPMC6345623 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genome-wide analyses and functional profiling of human NK cell lines.

Gunesch Justin T JT Angelo Laura S LS Mahapatra Sanjana S Deering Raquel P RP Kowalko Johanna E JE Sleiman Patrick P Tobias John W JW Monaco-Shawver Linda L Orange Jordan S JS Mace Emily M EM

Molecular immunology 20180724

Natural killer (NK) cell lines, including YTS, NK92, NK3.3, and NKL, represent excellent models for the study of human natural killer cells. While phenotypic and functional differences between these cell lines have been reported, a multi-parametric study, encompassing genomic, phenotypic, and functional assays, has not been performed. Here, using a combination of techniques including microarray and copy number analyses, flow cytometry, and functional assays, we provide in-depth genetic, function ...[more]

PMID: 30054012

Similar Datasets

Project description:BackgroundExpression level of many genes shows abundant natural variation in human populations. The variations in gene expression are believed to contribute to phenotypic differences. Emerging evidence has shown that microRNAs (miRNAs) are one of the key regulators of gene expression. However, past studies have focused on the miRNA target genes and used loss- or gain-of-function approach that may not reflect natural association between miRNA and mRNAs.Methodology/principal findingsTo examine miRNA regulatory effect on global gene expression under endogenous condition, we performed pair-wise correlation coefficient analysis on expression levels of 366 miRNAs and 14,174 messenger RNAs (mRNAs) in 90 immortalized lymphoblastoid cell lines, and observed significant correlations between the two species of RNA transcripts. We identified a total of 7,207 significantly correlated miRNA-mRNA pairs (false discovery rate q<0.01). Of those, 4,085 pairs showed positive correlations while 3,122 pairs showed negative correlations. Gene ontology analyses on the miRNA-correlated genes revealed significant enrichments in several biological processes related to cell cycle, cell communication and signal transduction. Individually, each of three miRNAs (miR-331, -98 and -33b) demonstrated significant correlation with the genes in cell cycle-related biological processes, which is consistent with important role of miRNAs in cell cycle regulation.Conclusions/significanceThis study demonstrates feasibility of using naturally expressed transcript profiles to identify endogenous correlation between miRNA and miRNA. By applying this genome-wide approach, we have identified thousands of miRNA-correlated genes and revealed potential role of miRNAs in several important cellular functions. The study results along with accompanying data sets will provide a wealth of high-throughput data to further evaluate the miRNA-regulated genes and eventually in phenotypic variations of human populations.

Project description:BackgroundEpstein-Barr virus (EBV) establishes lifelong infections in its human host. The virus is associated with a broad range of malignancies of lymphoid and epithelial origin, including Burkitt's lymphoma, post-transplant lymphoproliferative disease, nasopharyngeal carcinoma and gastric carcinoma. During the latent phase of its life cycle, EBV expresses more than 40 mature miRNAs that are highly abundant in tumor cells and may contribute to oncogenesis. Although multiple studies have assessed the relative expression profiles of EBV miRNAs in tumor cells, data linking these expression levels to functional target knockdown are mostly lacking. Therefore we set out to systematically assess the EBV miRNA expression levels in EBV(+) tumor cell lines, and correlate this to their functional silencing capacity in these cells.ResultsWe provide comprehensive EBV miRNA expression profiles of the EBV(+) cell lines C666-1 (nasopharyngeal carcinoma), SNU-719 (gastric carcinoma), Jijoye (Burkitt's lymphoma), and AKBM (Burkitt's lymphoma) and of EBV(-) cells ectopically expressing the BART miRNA cluster. By deep sequencing the small RNA population and conducting miRNA-reporter experiments to assay miRNA potency, we were able to compare the expression profiles of the EBV miRNAs with their functional silencing efficacy. We observe a strong correlation between miRNA expression levels and functional miRNA activity. There is large variation in expression levels between EBV miRNAs in a given cell line, whereas the relative expression profiles are well maintained between cell lines. Furthermore, we show that miRNA arm selection bias is less pronounced for gamma-herpesvirus miRNAs than for human miRNAs.ConclusionWe provide an in depth assessment of the expression levels and silencing activity of all EBV miRNAs in B- and epithelial cell lines of different latency stages. Our data show a good correlation between relative EBV miRNA expression levels and silencing capacity, and suggest preferential processing of particular EBV miRNAs irrespective of cell-type. In addition to encoding the largest number of precursor miRNAs of all human herpesviruses, EBV expresses many miRNAs precursors that yield two functional miRNA strands, rather than one guide strand and a non-functional passenger strand. This reduced strand bias may increase the size of the EBV miRNA targetome.

Dataset Information

Genome-wide analyses and functional profiling of human NK cell lines.

Publications

Genome-wide analyses and functional profiling of human NK cell lines.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets