Expression profiles of human NK cell subsets
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE57479 | GEO | 2017/01/01
SECONDARY ACCESSION(S): PRJNA246533
REPOSITORIES: GEO
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Project description:Pooled purified peripheral blood derived CD56dimCD16+ NK, CD56brightCD16- NK and in vitro activated CD56+CD16+ NK subsets obtained from 9 healthy donors were analyzed for gene expression pattern. Each pooled NK subset sample was hybridized in replicates (A and B). Keywords: other
2004-08-02 | GSE1511 | GEO
Project description:Natural killer cells are cytotoxic innate lymphoid cells that play an important role for early host defenses against infectious pathogens and surveillance against tumor growth and metastasis. In humans, NK cells may be divided in various subsets on the basis of the relative expression of the CD56 molecule and of the low-affinity FcγRIIIA CD16. In particular, the two main NK cell subsets are represented by the CD56bright CD16-/dull and the CD56dull CD16bright NK cells. A number of experimental evidences indicate that CD56bright and CD56dull NK cells represent different maturative stages of the NK cell developmental pathway. In an effort to identify NK cell miRNA signatures that may contribute to the NK cell-specific maturation program, we determined the miRNA profile of human NK cell subpopulations derived from peripheral blood samples of healthy donors. We identified multiple miRNAs that are differentially expressed in CD56bright CD16- and CD56dull CD16bright NK cells. Among these, we found a few miRNAs with a consistent differential expression in the two NK cell subsets, and with an intermediate expression in the CD56brightCD16dull NK cell subset, representing a transitional step of maturation of NK cells. Our data have been confirmed by both quantitative real-time PCR and multivariate analysis. These analyses allowed us to establish the existence of a miRNA signature able to discriminate the two main NK cell subsets, regardless of their surface phenotype. In addition, by analyzing the putative targets of representative miRNAs we show that miR-146a-5p, that displays a significant up-regulation in CD56bright as compared to CD56dull NK cells, may be involved in the regulation of killer Ig-like receptor (KIR) expression. These findings may contribute to a better understanding of the physiologic significance of miRNAs in the regulation of NK cell development/function. In addition, our results suggest that miR-146a-5p targeting, resulting in KIR down-regulation, may be exploited as a tool to generate/increment the effect of NK KIR-mismatching against HLA class I+ tumor cells and thus to improve the NK-mediated anti-tumor activity.
2018-11-06 | GSE116743 | GEO
Project description:Cord blood (CB)-derived chimeric antigen receptor (CAR)-natural killer (NK) cells targeting CD19 has been shown to be effective against B cell malignancies. While human CD56+ NK cells can be expanded in vitro, it is also known that NK cells can be differentiated from hematopoietic progenitor cells. It is still unclear whether CAR-NK cells are originated from mature NK cells or NK progenitor cells in CB. Here we found that CAR-NK cells are predominantly derived from the CD56- NK progenitor cells. We first found that substantial numbers of CD19 CAR-NK cells were produced from the CD56- CB mononuclear cells after in vitro culture for two weeks. Single cell RNAseq analysis of CD56-CD3-CD14-CD19- CB mononuclear cells revealed that those cells were subdivided into three subpopulations based on the expression of CD34 and HLA-DR. NK cells were predominantly produced from the CD34-HLA-DR- cells. In addition, in the CD34-HLA-DR- cells, only CD7+ cells could differentiate into NK cells. These results indicate that CD56-CD7+CD34- HLA-DR-lineage marker (Lin)- cells are the major origin of human CB-derived CAR-NK cells, indicating that we need to develop methods to enhance the quality and quantity of NK cells produced from these NK cell progenitor cells.
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Project description:Human NK cells from the decidua basalis of gravid uteri (dNK) and from cycling endometrium (eNK) of women undergoing hysterectomy were isolated and compared by gene expression profiling using Affymetrix microarrays with probes representing ~47,400 transcripts. Substantial differences indicate that these two types of NK cells represent distinct subsets. Freshly isolated NK cells were obtained by FACS sorting. 4 dNK and 5 eNK samples were obtained form independent donors. dNK cells were isolated from the decidua basalis of first trimester placentas and sorted as CD3-, CD16-, CD56+ cells. eNK cells were obtained from non-affected regions of cycling endometrium of donor women undergoing hysterectomy and were sorted as CD45+, CD56+, CD3- cells . The preliminary patient diagnoses included genital prolapse, fibroids, cervical dysplasia, or menorrhagia. All cycling endometrium samples were from the secretory phase of the cycle with exception of sample eNK_S6 that was from the proliferative phase.
2010-03-09 | E-GEOD-20499 | biostudies-arrayexpress
Project description:The mechanisms underlying human natural killer (NK) cell phenotypic and functional heterogeneity are unknown. Here, we have described the emergence of diverse subsets of human NK cells selectively lacking expression of signaling proteins following cytomegalovirus (CMV) infection. The absence of B and myeloid cell-related signaling protein expression in these NK cell subsets correlated with promoter DNA hypermethylation. Genome-wide DNA methylation patterns were strikingly similar between CMV-associated adaptive NK cells and cytotoxic effector T cells, but differed from those of canonical NK cells. Functional interrogation demonstrated altered cytokine responsiveness in adaptive NK cells that was linked to reduced expression of the transcription factor PLZF. Furthermore, subsets of adaptive NK cells demonstrated significantly reduced functional responses to activated autologous T cells. The present results uncover a spectrum of epigenetically unique adaptive NK cell subsets that diversify in response to viral infection and have distinct functional capabilities compared to canonical NK cell subsets.
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Project description:There is limited knowledge on the origin and development of the ample spectrum of human NK cells, particularly of specialized NK subsets. Here, we characterized the NK cell progeny of CD34+DNAM-1bright CXCR4+ precursors that reside in healthy bone marrow and circulate in the peripheral blood (PB) of patients with chronic infections/inflammation. including HIV, HCV or HCMV reactivation after HSC transplantation. Unlike conventional CD34+ precursors they rapidly differentiated in vitro into cytotoxic, IFNγ-secreting CD94/NKG2C+KIR+CD57+ maturing NK cell progenies with HCMV-inhibiting activity. Progeny characterization led also to identification of an additional new PB Lin-CD56-CD16+ precursor giving rise to the same CD94/NKG2C+KIR+CD57+ maturing NK cell progenies. Microarray analysis of NK cell progenies revealed a signature compatible with maturing adaptive NK cells. In vivo circulation of multiple common lymphocyte precursors with rapid development to NKG2C+ NK cell progeny is steadily occurring and may thus be a crucial resource for the prompt control of HCMV. We used microarray to compare the transcriptional profiles of human NKG2C+ NK cells derived from i) CD34+DNAM1brightCXCR4+ precursors, ii) Lin-CD34-CD16+CD56- precursors, iii) peripheral blood.
2020-12-31 | GSE136570 | GEO
Project description:Whole transcriptome of TR3-56, NK, CD3+CD56- and CD8+ cell subsets
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Project description:We sorted Eomes-negative NK cells (CD3- CD56+ CXCR6- CD16-) and Eomes-positive NK cells (CD3- CD56+ CXCR6+) from total leukocytes isolated from the perfusion fluid of five healthy human livers destined for transplantation. Total RNA was extracted from sorted cells, cDNA generated and RNASeq performed.
2016-09-28 | GSE87392 | GEO
Project description:In this study, we aim to establish the means to characterize cynomolgus macaque natural killer (NK) cells, and to investigate the CD27/CD11b NK maturation model in Macaca fascicularis NK cell subpopulations. The NK development studies performed mainly in mice models have demonstrated four functionally distinct subsets as defined by CD27 and CD11b, however this has not yet been established in nonhuman primates. The expression data of these macaque NK subsets will be associated with the antibody-dependent cellular cytotoxicity and missing-self responses produce by each subset.
2019-12-01 | GSE135836 | GEO
Project description:Natural killer (NK) cells can be grouped into distinct subsets that are localized to different organs and exhibit different capacity to secrete cytokines and mediate cytotoxicity. Despite these hallmarks that reflect tissue-specific specialization in NK cells, little is known about the factors that control the development of these distinct subsets. The basic leucine zipper transcription factor nuclear factor interleukin 3 (Nfil3; E4bp4) is essential for bone marrow-derived NK cell development but it is not clear whether Nfil3 is equally important for all NK cell subsets nor how it induces NK lineage commitment. Here we show that Nfil3 is required for the formation of Eomesodermin (Eomes)-expressing NK cells, including conventional medullary and thymic NK cells, whereas TRAIL+ Eomes- NK cells develop independent of Nfil3. Loss of Nfil3 during the development of bone marrow-derived NK cells resulted in reduced expression of Eomes and, conversely, restoration of Eomes expression in Nfil3-/- progenitors rescued NK cell development and maturation. Collectively, these findings demonstrate that Nfil3 drives the formation of mature NK cell by inducing Eomes expression and reveal the differential requirements of NK cell subsets for Nfil3. RNA-sequencing of natural killer (NK) cell subsets
2014-05-07 | E-GEOD-54291 | biostudies-arrayexpress