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Analysis of the transcriptome of human NK lymphocytes

dc.contributor.advisorWalter, Lutz Prof. Dr.
dc.contributor.authorZaitseva, Olena
dc.titleAnalysis of the transcriptome of human NK lymphocytesde
dc.contributor.refereeWalter, Lutz Prof. Dr.
dc.description.abstractengNatural Killer cells are large granular lymphocytes that contribute to both innate and adaptive immunity, as they can not only lyse infected cells or tumors, but also stimulate an adaptive immune response via production of cytokines and chemokines. NK cells function at the frontline of defense against intracellular pathogens and transformed cells due to their ability to respond rapidly and without prior sensitization on multiple signals. Traditionally the knowledge about NK cell function and development was obtained mainly from mouse models, transplantations and in vitro studies, but development of high throughput methods of gene expression analysis in the last years shed more light on NK cell developmental and functional diversity as well as on ontological relations between their subpopulations. However, our knowledge about NK cells remains incomplete, especially in comparison to T and B lymphocytes, and many questions in this field are yet to be answered. Together with our collaborators, our group collected an RNA-seq data set that, to our knowledge, is the most complete available for NK cell populations. This data set was comprehensively analyzed to elucidate the specific feature of transcriptomes of developing and mature NK cells. Typical transcription signature of NK cells that distinguishes them from other peripheral blood mononuclear cells (PBMCs) and changes in expression profiles of NK cells during their development was described. In particular, a set of novel genes was identified in which specific expression or function in NK cells was not described before. Differences in expression profiles of NK cells from tissues and functional groups were also described, in particular the relative immature phenotype of bone marrow-derived stage 3 NK populations in comparison to their counterparts in tonsils. Further, more mature and activated phenotype of NK cells produced by in vitro differentiation assays in comparison to their ex vivo counterparts was stated, which can be explained by using a cytokine cocktail for proper growth and development of cells in vitro. In addition, expression levels of non-protein coding genes expressed by NK cells were estimated and the set of non-protein coding genes with regulatory potential in development and function of NK cells (e.g. LINC00299, RP11-222K16.2, RP11-212I21.4, RP11-456D7.1, RP11-121A8.1) was identified. Furthermore, the single cell expression analysis of mature human NK lymphocytes using the microfluidic Fluidigm© technique was established and a pilot experiment was performed, which allows further estimation of heterogeneity level of mature NK cell, identification of their functional subpopulations, and studying of regulatory gene networks within
dc.contributor.coRefereeStülke, Jörg Prof. Dr.
dc.contributor.thirdRefereeDobbelstein, Matthias Prof. Dr.
dc.subject.engNK lymphocytesde
dc.affiliation.instituteGöttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)de
dc.subject.gokfullBiologie (PPN619462639)de

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