Similar Datasets
Project description:Innate lymphocytes in solid human tumors
| PRJNA863562 | ENA
Project description:γδ T lymphocytes represent ~1% of human PBMC and even more cells in most tissues of vertebrates. Although they have important anticancer functions, most current scRNA-Seq studies do not identify γδ T lymphocytes since their transcriptomes at the single cell level are unknown. Here we show that high resolution clustering of large scRNA-Seq data sets and a combination of gene signatures allow the specific detection of human γδ T lymphocytes and identification of their TCRVδ1 and TCRVδ2 subsets in large data sets from complex cell mixtures. In t-SNE plots from blood and tumor samples, the few γδ T lymphocytes appear collectively embedded between cytotoxic CD8 T and NK cells. Their TCRVδ1 and TCRVδ2 subsets form close yet distinct sub-clusters respectively neighbouring NK and CD8 T cells owing to expression of shared and distinct cytotoxic maturation genes. Similar pseudo-time maturation trajectories of TCRVδ1 and TCRVδ2 γδ T lymphocytes were discovered, unveiling in both subsets an unattended pool of TEMRA cells with preserved proliferative capacity, a finding confirmed by in vitro proliferation assays. Overall, the single cell transcriptomes of thousands of individual gd T lymphocytes from different CMV+ and CMV- donors reflect cytotoxic maturation stages driven by the immunological history of donors. This landmark study establishes the rationale for identification, subtyping and deep characterization of human γδ T lymphocytes in further scRNA-Seq studies of complex tissues in physiological and disease conditions.
2019-05-01 | GSE128223 | GEO
Project description:Innate lymphocytes encompass a diverse array of phenotypic identities with specialized effector functions. DNA methylation and hydroxymethylation are essential mechanisms for epigenetic fidelity and fate commitment. The landscapes of these modifications are unknown in innate lymphocytes. Here, we characterized the whole-genome distribution of methyl-CpG and 5-hydroxymethylcytosine (5hmC) in mouse ILC3, ILC2, and NK cells. We identified differentially methylated and hydroxymethylated DNA regions between ILC-NK subsets and correlated them with signature transcriptional modules. We associated lineage-determining transcription factors with demethylation and demonstrated unique patterns of DNA methylation/hydroxymethylation in relationship to open chromatin regions, histone modifications, and transcription factor binding sites. We also discover a novel association between 5hmC and NK cell super-enhancers. Using Tet2-deficient mice, we showed that the DNA hydroxymethylase Tet2 is required for optimal production of hallmark cytokines by ILC3 and production of IL-17A by inflammatory ILC2. These findings provide a powerful resource for studying immune epigenetic regulation and further decode the regulatory logic governing innate lymphocyte identity.
2022-02-16 | GSE190944 | GEO
Project description:We performed low input RNA-seq and single-cell RNA-seq to transcriptionally characterize four human innate T cell (ITCs) subsets, namely iNKT, MAIT, Vδ1 expressing γδ T cells, and Vδ2 expressing γδ T cells. We compared ITCs to CD4+ T and CD8+ T cells, representing the adaptive compartment, and to Natural Killer (NK) cells, representing the innate compartment.
2019-01-08 | GSE124731 | GEO
Project description:The following lymphocytes were sorted from the lamin propria of the small intestine of EomesGfg/+ RORgtCreTGg Rosa26Yfp/+ by using the markers Lineage- CD45+ Nkp46+ NK1.1+ : 1.convential NK cells (Eomes GFP+ RORgt YFP-) 2. ILC1 (Eomes GFP- RORgt YFP-) 3. exRORgt ILC3 (Eomes GFP- RORgt YFP+). Conventional NK cells from the bone marrow (cNK BM) were sorted from Eomes Gfp/+ mice with the markers Lineage- CD45+ NK1.1+ Eomes GFP+.
2014-04-15 | E-MTAB-2428 | biostudies-arrayexpress
Project description:We report differential gene expression in human peripheral blood NK cell enriched cytokine activated NKp65+ vs NKp65- innate lymphocytes.
2021-07-01 | GSE133772 | GEO
Project description:Natural Killer (NK) cells and CD8+ T cells share many characteristics at steady state and during viral infection. In this study, we interrogate the metabolic pathways that fuel NK cell effector function in response to mouse cytomegalovirus (MCMV) infection. This dataset contains transcriptional profiling of wild-type and LDHA-deficient Ly49Hpositive NK cells at steady state and early after infection.
2020-04-28 | GSE149447 | GEO
Project description:Malignancy can be suppressed by the immune system in a process termed immunosurveillance. However, to what extent immunosurveillance occurs in spontaneous cancers and the composition of participating cell types remain obscure. Here we show that cell transformation triggers a tissue-resident lymphocyte response in oncogene-induced murine cancer models. Non-circulating cytotoxic lymphocytes, derived from innate, TCRαβ and TCRγδ lineages, expand in early tumors. Characterized by high expression of NK1.1, CD49a and CD103, these cells share a gene expression signature distinct from those of conventional NK cells, T cells and invariant NKT cells. Generation of these lymphocytes is dependent on the cytokine IL-15, but not the transcription factor Nfil3 that is required for the differentiation of tumor-infiltrating NK cells; and IL-15, but not Nfil3, deficiency results in accelerated tumor growth. These findings reveal a novel tumor-elicited cancer immunosurveillance mechanism that engages unconventional type 1-like innate lymphoid cells and type 1 innate-like T cells.
2016-01-21 | GSE76362 | GEO
Project description:Mucosal-Associated Invariant T cells (MAIT cells) have a unique specificity for the microbial metabolite 5-OP-RU presented by the non-classical presentation molecule MR1. Upon activation, they release cytotoxic mediators and engage an antimicrobial activity. As a subset of T lymphocytes, MAIT development occurs in the thymus where they acquire their effector phenotype under the control of the key transcription factor ZBTB16. This particular maturation process is in contrast with conventional T cells that egress the thymus with a naive phenotype before populating the secondary lymphoid organs, and the molecular events driving the MAIT lineage decision are poorly known. In the present work, we evaluated the transcriptional events and the role of the slam-SAP pathway on the lineage decision of MR1-restricted T cells by single cell RNAseq. MAIT cells undergoing positive selection were FACS-sorted with a MR1:5-OP-RU labeled tetramer, from thymus of wild-type and sapKO mice. Their transcriptomes were captured using a 10x chromium system.
2019-07-01 | E-MTAB-7704 | biostudies-arrayexpress
Project description:Group 1 innate lymphoid cells (ILC1s) are cytotoxic and interferon gamma-producing lymphocytes lacking antigen-specific receptors, which include ILC1s and natural killer (NK) cells. In mice, ILC1s differ from NK cells, as they develop independently of the NK-specifying transcription factor EOMES, while requiring the repressor ZFP683 (ZNF683 in humans) for tissue residency. Here we identify highly variable ILC1 subtypes across tissues through investigation of human ILC1 diversity by single-cell RNA sequencing and flow cytometry. The intestinal epithelium contained abundant mature EOMES− ILC1s expressing PRDM1 rather than ZNF683, alongside a few immature TCF7+PRDM1− ILC1s. Other tissues harbored NK cells expressing ZNF683 and EOMES transcripts; however, EOMES protein content was variable. These ZNF683+ NK cells are tissue-imprinted NK cells phenotypically resembling ILC1s. The tissue ILC1-NK spectrum also encompassed conventional NK cells and NK cells distinguished by PTGDS expression. These findings establish a foundation for evaluating phenotypic and functional changes within the NK-ILC1 spectrum in diseases.
2024-06-14 | GSE240441 | GEO