In vitro differentiated CD56-positive ILC transcriptional profiling via scRNA-seq
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PROVIDER: PRJNA986935 | ENA |
REPOSITORIES: ENA
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Project description:The innate cytotoxic Natural Killer (NK) cells emerged during hematopoiesis through a linear model of human NK development, yet how in vitro model of NK differentiation recapitulates in vivo process is largely under-explored. Here, we established that NK cell trajectory in vitro can be divided into 4 stages by sequential acquisition of CD161, CD56 and CD94 in which CD56 bifurcation can separate Stage 3a (CD56-) as ILC-precursor that can further give rise to stage 3b (CD56+) and stage 4 (CD94+). Re-plating results together with clonal tracing between S3b, S4 and ILC3 subsets supported a diverging developmental point between NK and ILC3 lineages occurs at the S3a stage and accompanied by the loss of the ILC3 potential as NK cell maturation progress from S3b toward S4. Single-cell transcriptomic and RNA-velocity connected the NK cytotoxic trajectory with a coordinated network of transcription factors (TFs) that are highly compatible with primary NK cell gene program.
2023-06-30 | GSE235708 | GEO
Project description:Immunotherapies have had unprecedented success for multiple cancer types, albeit with variable response rates. Unravelling the complex network of immune cells within the tumour microenvironment (TME) may provide additional insights to enhance anti-tumour immunity and improve clinical response. Here, we identified a CD103-expressing CD56+ ILC subset that were associated with a poor proliferative capacity of tumour-infiltrating lymphocytes (TILs) in culture. We demonstrate that CD103+CD56+ ILCs isolated directly from tumors represent a distinct ILC population that expressed unique surface markers, transcription factor networks, and transcriptomic profiles compared to CD103-CD56+ NK cells. Using multiple approaches, we found that these CD103+CD56+ ILCs were associated with CD8+ T cells with a reduced expression of GZMB. This study identifies 59 a population of CD103+CD56+ ILCs with potentially inhibitory functions, that are associated with a TME that includes CD8+ T cells with poor anti-tumour activity. Further studies focusing on these potentially inhibitory cells may provide insights into understanding the biology of an inhibitory TME.
2024-09-07 | GSE276563 | GEO
Project description:Human blood innate lymphoid cells (ILCs), which include ILCs and natural killer (NK) cells, derive from a common CD117+ILC precursor (ILCP). Yet, the relationship among the ILC subsets remains unclear. Bulk and single cell RNA-Seq and ATAC-Seq showed that blood ILC subsets cluster into ILC2s, ILCPs, a mixed cluster of CD56dim and CD56– NK cells, and a separate cluster of CD56hiNK cells that shares features with both ILCs and CD56dim/–NK cells. In surprising contrast to mice, tissue repair protein amphiregulin (AREG) was produced by human NK cells, with even higher levels in CD56hiNK cells than in ILCs. AREG expression in NK cells was driven by TCF7/WNT signaling and inhibited by TGFB1, a cytokine elevated in HIV-1+ people. Knockout of RUNX3, a WNT antagonist acting downstream of TGFB1, increased AREG production. Consistent with these findings, AREG+NK cells were decreased in people living with HIV-1. Additionally, functionally defective CD56–NK cells expanded in HIV-1+ people, in inverse correlation with CD56dimNK cells, ILCs, and CD4+T cells. Experiments in tissue culture and in humanized mice showed that CD56–NK cells derive from the epigenetically similar CD56dimNK cells, and that stimulation of MTOR by CD4+T cells or exogenous IL-2 prevents their expansion. These findings clarify how ILC subsets are related to each other and provide insight into how HIV-1 infection disrupts ILC homeostasis and contributes to pathology
2023-06-07 | GSE203002 | GEO
Project description:A small subset of T cells also expresses kiler-cell immunoglobulin-like receptors (KIRs). We find that KIR+ T cells primarily reside in the CD56+ T population. However, little is known on how these cells are different from the conventional CD56- T, NK, and iNKT cells. We used microarray profiling to compare and determine the distinctive differences of CD56+ T cell and its KIR subsets when compared to the conventional CD56- T, NK and iNKT cells. Lymphocyte subsets were sorted from human peripheral blood mononuclear cells with FACSAriaII (BD Biosciences, San Jose, CA) using anti-CD3, anti-CD56, anti-CD14, anti-KIR2DL1, anti-KIR2DL2/3, anti-KIR3DL1 and anti-TCRValpha24 antibodies. The purity of CD3+CD56- T cells, CD3-CD56+ NK cells, CD3+CD56+ T cells, KIR-CD3+CD56+ T cells, and KIR+CD3+CD56+ T cells were more than 98% in all experiments. The purities of iNKT cells for TCRValpha24 and CD1d-tetramer were >95% and >90%, respectively. RNA pre-amplification, labeling and hybridization on Human Genome U133Plus 2.0 GeneChip array were performed in the St. Jude Hartwell Center for Bioinformatics & Biotechnology microarray core facility according to the manufacturer’s instructions (Affymetrix, Santa Clara, CA).
2013-07-01 | E-GEOD-47855 | biostudies-arrayexpress
Project description:A small subset of T cells also expresses kiler-cell immunoglobulin-like receptors (KIRs). We find that KIR+ T cells primarily reside in the CD56+ T population. However, little is known on how these cells are different from the conventional CD56- T, NK, and iNKT cells. We used microarray profiling to compare and determine the distinctive differences of CD56+ T cell and its KIR subsets when compared to the conventional CD56- T, NK and iNKT cells.
2013-07-01 | GSE47855 | GEO
Project description:Innate lymphoid cells (ILC) represent innate versions of T helper and cytotoxic T cells that differentiate from committed ILC precursors (ILCP). Still, how ILCP relate to mature tissue-resident ILCs remains unclear. We observed that a population of CD117+ ILC from peripheral blood (PB) of healthy donors does not represent any conical ILC subset, but expressed marker (CD117) commonly expressed by hemato-lymphoid progenitors. We therefore hypothesized PB CD117+ ILC might include uncommitted lymphoid precursors. In order to further understand the identity of PB CD117+ ILC, we profiled the transcriptome of highly purified circulating CD117+ ILC compared to CD34+ HSC, the latter representing immature hematopoietic progenitors with multi-lineage potential. Clear differences in gene expression profiles emerged, with a large cluster of 1540 genes expressed at substantially higher levels in CD117+ ILC. In contrast, CD34+ HSC cells highly expressed genes involved in the broad development of diverse hematopoietic lineages. Compared to HSC, CD117+ ILC express high levels of TF that have been shown to be essential for murine ILC development and we did not detect transcripts characteristic of T and B cells development. Transcriptomic analysis suggested that CD117+ ILC represent lymphoid-biased progenitors carrying a TF expression profile resembling a multi-potent ILC precursor (ILCP).
2017-03-19 | GSE90834 | GEO
Project description:scRNA-seq of in vitro differentiated D6 mPGCLCs
| PRJNA809820 | ENA
Project description:In chronic inflammatory diseases with an autoimmune component like atherosclerosis, some regulatory T cells (Tregs) lose their regulatory function and become exTregs. The present study was designed to identify surface markers specific of human exTregs, using an integrated approach from sorted mouse exTregs bulk RNA-Seq to human scRNA-Seq with CITE-Seq, to sort human exTregs and characterize them by transcriptome and function. We crossed inducible Treg lineage tracker mice (FoxP3-eGFP-Cre-ERT2 ROSA26CAG-fl-stop-fl-tdTomato) to atherosclerosis-prone Apoe -/- mice, sorted Tregs and exTregs from lymph nodes and spleens of replicate mice and determined their transcriptomes by bulk RNA sequencing (RNA-Seq). A support vector machine (SVM) approach identified the leading signature genes for exTregs as CST7, NKG7, GZMA, PRF1, TBX21 and CCL4. Projecting these genes onto feature maps of human PBMC single cell (sc)RNA-Seq with CITE-Seq from 61 subjects with and without atherosclerosis showed that CST7, NKG7, GZMA, PRF1, TBX21 and CCL4 mapped to CD4 T cells that expressed CD56 and CD16. This finding was validated in a second, independent scRNA- and CITE-Seq dataset. Even in healthy volunteers, a subpopulation of CD4 T cells expressed both CD56 and CD16. Bulk RNA-Seq identified these cells as cytotoxic CD4 T cells, which was functionally confirmed in a cell killing assay. DNA sequencing for TCRβ showed clonal expansion of Treg CDR3 sequences in CD16 + CD56 + exTregs. Taken together, we identify mouse and human exTregs as cytotoxic CD4 T cells.
2023-07-25 | GSE217010 | GEO
Project description:Subtypes of innate lymphoid cells (ILC), defined by effector function and transcription factor expression, have recently been identified. In the adult, ILC derive from common lymphoid progenitors in bone marrow, although transcriptional regulation of the developmental pathways involved remains poorly defined. TOX is required for development of lymphoid tissue inducer cells, a type of ILC3 required for lymph node organogenesis, and NK cells, a type of ILC1. We show here that production of multiple ILC lineages requires TOX, as a result of TOX-dependent development of common ILC progenitors. Comparative transcriptome analysis demonstrated failure to induce various aspects of the ILC gene program in the absence of TOX, implicating this nuclear factor as a key early determinant of ILC lineage specification. TOX KO vs. wild tyype
2015-04-27 | E-GEOD-65850 | biostudies-arrayexpress
Project description:Background: Innate lymphoid cells (ILCs) comprise cytotoxic NK cells and “helper” ILCs (hILCs). Human hILC development is less characterized as compared to NK cells, although all ILCs are developmentally related. It has been reported that the immunosuppressive drugs glucocorticoids (GCs) regulate ILCs function, but whether they control ILCs differentiation from hematopoietic stem cells (HSCs) is unknown. Objective: We sought to analyze the effect of GCs on ILC development from HSCs. Methods: We exploited an in vitro system to generate and expand from peripheral blood (PB) HSCs a multipotent CD56+ ILC precursor able to differentiate into NK cells, ILC1s and ILC3s. We also analyzed ex vivo, at different time points, the PB of allogeneic HSC transplantation (HSCT) recipients who were or were not treated with GCs and compared ILC subset reconstitution. Results: We show that, in vitro, GCs favor the generation of NK cells from myeloid precursors, while they strongly impair lymphoid development. In support to these data, HSCT recipients who had been treated with GCs display a lower number of circulating hILCs, including the ILCP previously identified as a systemic substrate for tissue ILC differentiation. Conclusions: GCs impair the development of the CD117+ ILCP from CD34+ HSCs, while they do not affect the further steps of ILCP differentiation towards NK cells and hILC subsets. This reflects an association of GC treatment with a marked reduction of circulating hILCs in the recipients of HSCT.
2021-11-05 | GSE186950 | GEO