Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA382743 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5445420_1.fastq.gz | Fastqsanger.gz | |||
| SRR5445420_2.fastq.gz | Fastqsanger.gz | |||
| SRR5445430_1.fastq.gz | Fastqsanger.gz | |||
| SRR5445430_2.fastq.gz | Fastqsanger.gz | |||
| SRR5445440.fastq.gz | Fastqsanger.gz |
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Project description:HIV-1 permanently disrupts homeostatic ILCs and expands inflammatory TCF7-dependent memory NK cells
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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:The development of innate lymphoid cell (ILC) transcription factor reporter mice has shown a previously unexpected complexity in ILC haematopoiesis. Using novel polychromic mice to achieve higher phenotypic resolution we have characterised bone marrow progenitors that are committed to the group 1 ILC lineage. These common ILC1/NK progenitors, which we call ‘aceNKPs’, are defined as lineage–Id2+IL-7Ra+CD25–a4b7–NKG2A/C/E+Bcl11b–. In vitro, aceNKPs differentiate into group 1 ILCs, including NK-like cells that express Eomes without the requirement for IL-15, and produce IFN-g and perforin upon IL-15 stimulation. Following reconstitution of Rag2–/–Il2rg–/– hosts, aceNKPs give rise to a spectrum of mature ILC1/NK cells (regardless of their tissue location) that cannot be clearly segregated into the traditional ILC1 and NK subsets, suggesting that group 1 ILCs constitute a dynamic continuum of ILCs that can develop from a common progenitor. In addition, aceNKP-derived ILC1/NK cells effectively ameliorate tumour burden in a model of lung metastasis where they acquired a cytotoxic NK cell phenotype. Our results identify the primary ILC1/NK progenitor that lacks ILC2 or ILC3 potential and is strictly committed to ILC1/NK cell production irrespective of tissue homing.
2022-11-02 | GSE213814 | GEO
Project description:In an era where the established lines between cell identities are blurred by intra-lineage plasticity, distinguishing between stable and transitional states becomes imperative. This challenge is particularly pronounced within the Group 1 ILC lineage, where the similarity and plasticity between NK cells and ILC1s obscure their classification and the assignment of their unique contributions to immune regulation. This study exploits the unique property of AsGM1—a membrane lipid associated with cytotoxic attributes absent in ILC1s—as a definitive criterion to distinguish between these cells. By prioritizing cytotoxic potential as the cardinal differentiator, the strategic use of this glycosphingolipid signature achieved precise delineation of the heterogenity of Group 1 ILCs across tissues. This capability extends beyond steady-state classifications, adeptly capturing the binary classification of NK cells and ILC1s during acute liver injury. By leveraging two established models of NK-to-ILC1 plasticity driven by TGFβ in endocrine tissues and Toxoplasma gondii infection, we demonstrate the stability of the AsGM1 signature during this reprogramming, which sharply contrasts with the loss of Eomes. The early detection of the AsGM1 signature at the immature NK (iNK) stage, preceding Eomes, and its stability, unaffected by transcriptional reprogramming that typically alters Eomes, position AsGM1 as a unique, site-agnostic marker for fate mapping NK-to-ILC1 plasticity. This provides a powerful tool to explore the expanding heterogeneity within the Group 1 ILC landscape, effectively transcending the ambiguity inherent to the NK-to-ILC1 continuum.
2025-02-05 | GSE269280 | GEO
Project description:Objective: Hepatocellular carcinoma (HCC) represents a typical inflammation-associated cancer. Tissue resident innate lymphoid cells (ILCs) have been suggested to control tumor surveillance. Here we studied how the local cytokine milieu controls ILCs in HCC. Design: We performed bulk RNA sequencing of HCC tissue as well as flow cytometry and single-cell RNA sequencing of enriched ILCs from non-tumor liver, margin and tumor core derived from 48 HCC patients. Simultaneous measurement of protein and RNA expression at the single-cell level (AbSeq) identified precise signatures of ILC subgroups. In-vitro culturing of ILCs was used to validate findings from in-silico analysis. Analysis of RNA-sequencing data from large HCC cohorts allowed stratification and survival analysis based on transcriptomic signatures. Results: RNA sequencing of tumor, non-tumor and margin identified tumor-dependent gradients of which were not only associated with poor survival but also control ILC plasticity. Single-cell RNA sequencing and flow cytometry of ILCs from HCC livers identified NK-like cells in the non-tumor tissue, losing their cytotoxic profile as they transitioned into tumor ILC1 and NK-like-ILC3 cells. Tumor ILC composition was mediated by cytokine gradients that directed ILC plasticity towards activated tumor ILC2s. This was liver-specific and not seen in ILCs from PBMC. Patients with high ILC2/ILC1 ratio expressed IL-33 in the tumor that promoted ILC2 generation which was associated with better survival. Conclusion: Our results suggest that the tumor cytokine milieu controls ILC composition and HCC outcome. Specific changes of cytokines modify ILC composition in the tumor by inducing plasticity and alter ILC function.
2021-08-11 | GSE179746 | GEO
Project description:Objective: Hepatocellular carcinoma (HCC) represents a typical inflammation-associated cancer. Tissue resident innate lymphoid cells (ILCs) have been suggested to control tumor surveillance. Here we studied how the local cytokine milieu controls ILCs in HCC. Design: We performed bulk RNA sequencing of HCC tissue as well as flow cytometry and single-cell RNA sequencing of enriched ILCs from non-tumor liver, margin and tumor core derived from 48 HCC patients. Simultaneous measurement of protein and RNA expression at the single-cell level (AbSeq) identified precise signatures of ILC subgroups. In-vitro culturing of ILCs was used to validate findings from in-silico analysis. Analysis of RNA-sequencing data from large HCC cohorts allowed stratification and survival analysis based on transcriptomic signatures. Results: RNA sequencing of tumor, non-tumor and margin identified tumor-dependent gradients of which were not only associated with poor survival but also control ILC plasticity. Single-cell RNA sequencing and flow cytometry of ILCs from HCC livers identified NK-like cells in the non-tumor tissue, losing their cytotoxic profile as they transitioned into tumor ILC1 and NK-like-ILC3 cells. Tumor ILC composition was mediated by cytokine gradients that directed ILC plasticity towards activated tumor ILC2s. This was liver-specific and not seen in ILCs from PBMC. Patients with high ILC2/ILC1 ratio expressed IL-33 in the tumor that promoted ILC2 generation which was associated with better survival. Conclusion: Our results suggest that the tumor cytokine milieu controls ILC composition and HCC outcome. Specific changes of cytokines modify ILC composition in the tumor by inducing plasticity and alter ILC function.
2021-08-11 | GSE179795 | GEO
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
Project description:Introduction: The role of innate lymphoid cells (ILC) in cancer and specifically in the context of hepatocellular carcinoma (HCC) is not well understood. Immune checkpoint inhibitors (ICI) have been approved for treatment of patients with HCC. The effect of ICI on ILCs has not been explored. Methods: We studied ILCs in PBMCs of 51 patients with HCC at baseline and after treatment with ICI. Flow cytometry was used to study ILC composition. Single-cell RNA-sequencing using a targeted panel of 405 immune-related genes was used to characterize the transcriptomic profiles as well as cellular trajectory of ILCs before and after ICI therapy. Intracellular cytokine staining was used to validate ILC function. Data from large patient cohorts were used to predict association with survival. Results: Characterization of the ILC subgroups in PBMCs of HCC patients revealed a significant increase in ILC1 and a decrease in ILC3 frequencies. Single cell RNA-sequencing identified a subgroup of NK-like ILCs which expressed cytotoxicity markers as well as NKp80/KLRF1. This KLRF1high-NK-like population showed low abundance in patients with HCC and was enhanced after combined anti-CTLA-4 and anti-PD-1 immunotherapy. Trajectory analysis placed this population in between ILC1 and ILC3s. The transcriptomic signature of KLRF1high NK-like ILCs was associated with better progression-free survival in HCC cohorts. Conclusions: We present a previously unknown effect of HCC tumors and ICIs on the composition and plasticity of ILCs in PBMCs. We identified a cytotoxic KLRF1high-NK-like subgroup which was associated with better survival, absent in untreated HCC patients, and enhanced upon ICI immunotherapy. Thus, ILCs from PBMC can be used to study changes in the innate immune system under immunotherapy.
2022-06-23 | GSE195648 | GEO
Project description:Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from NK cells is a gene signature indicative of TGFb-family cytokine imprinting. To assess the impact of TGFb family cytokines on ILC1 differentation, we examined SMAD4- a transcription factor that facilitates the signaling pathway common to all TGFb family cytokines-was specifically ablated in ILCs and NK cells. While SMAD4 deficiency did not affect ILC1 differentation, NK cells paradoxically aquired an ILC1-like gene signature and were incapable of controlling tumor metastasis and viral infection. We used microarray to define the transcriptional differences between splenic NK cells from WT and SMAD4F/F x Ncr1-Cre mice.
2017-07-31 | GSE100247 | GEO
Project description:Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from NK cells is a gene signature indicative of TGFb-family cytokine imprinting. To assess the impact of TGFb family cytokines on ILC1 differentation, we examined SMAD4- a transcription factor that facilitates the signaling pathway common to all TGFb family cytokines-was specifically ablated in ILCs and NK cells. While SMAD4 deficiency did not affect ILC1 differentation, NK cells paradoxically aquired an ILC1-like gene signature and were incapable of controlling tumor metastasis and viral infection. We used microarray to compare the transcriptional differences between human blood NK cells. NK cells from a patient with a deleterious SMAD4 mutation or control NK cells were cultured overnight with either IL-2 alone or TGFb1 and IL-2.
2017-07-31 | GSE100246 | GEO