Lineage heterogeneity underlies the multiple origins and functions of type 1 innate lymphoid cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE205894 | GEO | 2022/07/31
REPOSITORIES: GEO
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Project description:Lineage heterogeneity underlies the multiple origins and functions of type 1 innate lymphoid cells
| PRJNA848134 | ENA
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:The precise lineage relationships between innate lymphoid cells (ILC) and the lymphoid tissue inducer (LTi) are poorly understood. Using single-cell multiplex transcriptional analysis of 100 lymphoid genes and single-cell cultures of fetal liver precursor cells, we identified the common proximal precursor to these lineages and showed that its bifurcation was precisely marked by the differential induction of the transcription factors PLZF and TCF1. Acquisition of individual ILC1/2/3-specific effector programs was initiated later, at the common ILC precursor (ILCP) stage, by transient expression of mixed ILC1/2/3 transcriptional patterns whereas, in contrast, LTi development did not go through multilineage priming. These findings provide novel insights into divergent mechanisms of ILC and LTi lineage differentiation and establish a high-resolution map of their development.
2015-12-30 | GSE76407 | GEO
Project description:We provide a map of human ILC heterogeneity across multiple anatomical sites. Tissue-specific distinctions are particularly apparent for ILC1 populations, whose distribution was markedly altered in obesity or aging. Furthermore, the degree of ILC1 population hetero- geneity differed substantially in lymphoid versus mucosal sites. Together, these analyses comprise a comprehensive characterization of the spatial and temporal dynamics regulating the anatomical distri- bution, subset heterogeneity, and functional poten- tial of ILCs in non-diseased human tissues.
2019-02-06 | GSE126107 | 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:Purpose: Characterization of murine innate lymphoid cells (ILC) by next generation expression analysis Methods: Lymph node cells from Rorc(gt)-GFP reporter mice were independently sorted three times by flow cytometry to isolate ILC1, ILC2, ILC3 and lymphoid tissue inducer (LTi) cells. Subsequently RNA was prepared (Rneasy Micro Kit, Qiagen) and subjected to cDNA synthesis by using the SMART Seq v4 Ultra Low Input RNA Kit (Takara Bio) according to the manufacturer's protocol. Library preparation was performed with Nextera XT DNA Library Prep Kit (Illumina) and next generation sequencing was carried out on an Illumina HiSeq2500 using 50 bp single reads. Adapter contamination were removed by trim_galore and cutadapt from the sequence reads that passed quality filters (Phred score > 30). Resulting libraries were aligned to the mouse reference genome (GRCm38) using the RNA-seq aligner STAR with default parametrization. Reads aligned to annotated genes were quantified with the HTseq-count program using gene annotations from Ensembl release 81. The determined read counts served as input to DESeq2 for pairwise detection and quantification of differential gene expression. For DESeq2 parametrization we used a beta prior and disabled the Cook distance cutoff filtering. Results: The sequencing depth of our libraries varies between 25.5 and 39.2 million reads. The mapping rates for the libraries were found in the range between 93.9 and 98.0 %. Unsupervised hierarchical clustering of the top 50 differentially expressed genes show a close relationship of the samples within a group and higher similarity between ILC3 and LTi cells whereas ILC1 and ILC2 appear as separated populations. Among the differentially expressed genes we identified already described transcripts like Gzma (ILC1), Klrg1 (ILC2) and Il22 (ILC3, LTi) as well as uncharacterized genes that may play a role for the ILC lineage and function in lymphoid organs. Conclusions: We report a detailed next generation transcriptome analysis of ILC populations from murine lymph nodes. Our analysis helps to define the developmental status of ILC in secondary lymphoid organs, which might represent a precursor state that can be further modulated in tissues.
2021-05-31 | GSE168208 | GEO
Project description:Innate lymphoid cells (ILCs) play strategic roles in tissue homeostasis and immunity. ILCs arise from lymphoid progenitors undergoing lineage restriction leading to the development of specialised ILC subsets. We generated ‘5x polychromILC’ compound transcription factor reporter mice to delineate ILC precursor states by revealing the multifaceted expression of key ILC-associated transcription factors (Id2, Bcl11b, Gata3, Rorc(γt) and Rora) during ILC development in the bone marrow. This approach allowed previously unattained enrichment of rare progenitor subsets and revealed hitherto unappreciated ILC precursor heterogeneity. In vivo and in vitro assays identified novel precursors with potential to generate all ILC subsets and natural killer cells, and also permitted discrimination of elusive ILC3 bone marrow antecedents. Single cell gene expression analysis identified a discrete ILC2-committed population and delineated transition states between early progenitors and a highly heterogeneous ILC1/3/NK precursor cell cluster. This diversity may facilitate greater lineage potential upon progenitor recruitment to peripheral tissues.
2019-05-11 | GSE131038 | 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:This study examines the role of retinoic acid receptor (RAR) activity in type 1 innate lymphoid cells (ILC1s) by using Rosa26-RARα403 mice, that enable Cre-mediated inhibition of RAR activity in a dominant negative manner.
2022-07-31 | GSE205895 | GEO
Project description:Malignancy can be suppressed by the immune system. However, the classes of immunosurveillance responses and their mode of tumor sensing remain incompletely understood. Here, we show that while clear cell renal cell carcinoma (ccRCC) was infiltrated by exhaustion-phenotype CD8+ T cells which negatively correlated with patient prognosis, chromophobe RCC had abundant infiltration of granzyme A-expressing intraepithelial type 1 innate lymphoid cells (ILC1s) that positively associated with patient survival. Interleukin-15 (IL-15) promoted ILC1 granzyme A expression and cytotoxicity, and IL-15 expression in chRCC tumor tissue positively tracked with the ILC1 response. An ILC1 gene signature also predicted survival of a subset of breast cancer patients in association with IL-15 expression. Notably, ILC1s directly interacted with cancer cells, and IL-15 produced by cancer cells supported the expansion and anti-tumor function of ILC1s in a murine breast cancer model. Thus, ILC1 sensing of cancer cell IL-15 defines an immunosurveillance mechanism of epithelial malignancies.
2022-04-02 | GSE199798 | GEO