Similar Datasets
Project description:Innate lymphoid cells (ILCs) are highly plastic immune cells that have been separated into 3 main subsets, characterized by distinct phenotypic and functional profiles. Using single cell approaches, heightened heterogeneity of mouse ILCs has been recently appreciated, imprinted by tissue signals that shape their transcriptome and epigenome. Intra-subset diversity has also been observed in human ILCs. However, combined transcriptomic and epigenetic analyses of single ILCs in humans are lacking. Here we show high transcriptional and epigenetic heterogeneity among human circulating ILCs in healthy individuals. We describe phenotypically distinct subclusters within main circulating ILC populations. We show diverse chromatin accessibility within main ILC subsets, compatible with differentially poised states. We validate the use of this healthy donor-based analysis as resource dataset to infer ILC changes occurring in disease conditions. Overall, our work provides new insights in the complex human ILC biology. We anticipate our work to be a starting point to facilitate hypothesis-driven studies in patients, without the need to perform single cell OMICs using precious patients’ material
2023-09-01 | GSE225168 | GEO
Project description:Innate lymphoid cells (ILCs) are highly plastic immune cells that have been separated into 3 main subsets, characterized by distinct phenotypic and functional profiles. Using single cell approaches, heightened heterogeneity of mouse ILCs has been recently appreciated, imprinted by tissue signals that shape their transcriptome and epigenome. Intra-subset diversity has also been observed in human ILCs. However, combined transcriptomic and epigenetic analyses of single ILCs in humans are lacking. Here we show high transcriptional and epigenetic heterogeneity among human circulating ILCs in healthy individuals. We describe phenotypically distinct subclusters within main circulating ILC populations. We show diverse chromatin accessibility within main ILC subsets, compatible with differentially poised states. We validate the use of this healthy donor-based analysis as resource dataset to infer ILC changes occurring in disease conditions. Overall, our work provides new insights in the complex human ILC biology. We anticipate our work to be a starting point to facilitate hypothesis-driven studies in patients, without the need to perform single cell OMICs using precious patients’ material
2023-09-01 | GSE225167 | GEO
Project description:Innate lymphoid cells (ILCs) are part of the innate immune cell family. Three different subsets of ILCs, ILC1s, ILC2s and ILCPs can be identified in human peripheral blood. Based on their expression of transcription factors and cytokines, they are considered as being the innate counterparts of CD4 T helper subsets, namely Th1s, Th2s and Th17s. However, ILCs and Th cells have different roles in immunity. Therefore, we compared the transcriptomes of sorted ILC1s, ILC2s, ILCPs, Th1s, Th2s and Th17s from the peripheral blood of three different donors. RNA sequencing of ILC and Th subsets revealed differences in the expression of tens to hundreds of genes. These genes are involved in cell trafficking, innate activation and inhibitory functions. ILC and Th cell subsets also differ in their expressions of long-non coding RNAs.
2020-02-04 | E-MTAB-8494 | biostudies-arrayexpress
Project description:The functions of innate lymphoid cells (ILCs) in immune system are increasingly appreciated, whereas the early development of ILCs in human remains elusive. In this study, we sorted humanhematopoietic stem progenitor cells, lymphoid progenitors, presumed ILC progenitor/precursors and mature ILCs in the fetal hematopoietic, lymphoid and non-lymphoid tissues, from 8 to 12 PCW,for single-cell RNA-sequencing, followed by computational analysis and functional validation. We delineated the early phase of ILC development, from hematopoietic stem progenitor cells to multipotent lymphoid progenitors and to ILC progenitors, which mainly occurred in fetal liver and intestine. We further unveiled interleukin-3 receptor alpha (IL-3RA) as the surface marker for the lymphoid progenitors with T cell, B cell and ILC potentials. Notably, we determined the heterogeneity and tissue distribution of each ILC subpopulation, revealing the shared proliferating characteristics of the precursors of each ILC subtype. Additionally, a novel unconventional ILC2 subpopulation (CRTH2-CCR9+ ILC2) was identified in fetal thymus. Taken together, our study illuminates the precise cellular and molecular features underlying the stepwise formation of human fetal ILC hierarchy with remarkable spatiotemporal heterogeneity.
2021-08-09 | GSE163587 | GEO
Project description:Single cell RNAseq of human innate lymphoid cells (ILC)
| PRJNA471290 | ENA
Project description:The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127+ ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs, and signatures of tissue-residency, activation and modified metabolism in gut and lung ILCs. Trajectory analysis revealed potential differentiation pathways from circulating and tissue-resident naïve ILCs to a spectrum of mature ILC subsets. In the lung we identified both CRTH2+ and CRTH2- ILC2 with lung-specific signatures, which could be recapitulated by alarmin-exposure of circulating ILC2. Finally, we describe unique TCR-V(D)J-rearrangement patterns of blood ILC1-like cells, revealing a subset of potentially immature ILCs with TCR-d rearrangement. In summary, we provide publicly available data as a resource for in-depth understanding of ILC-mediated immunity in humans, with implications for disease.
2020-12-14 | GSE150050 | GEO
Project description:Innate lymphoid cells (ILCs) develop from common lymphoid progenitors (CLP), which further differentiate into the common ILC progenitor (CILP) that can give rise to both ILCs and NK cells. Murine ILC intermediates have recently been characterized, but the human counterparts and their developmental trajectories have not yet been identified, largely due to the lack of homologous surface receptors in both organisms. Here, we show that human CILPs (CD34+CD117+α4β7+Lin-) acquire CD48 and CD52, which define NK progenitors (NKPs) and innate lymphoid cell precursors (ILCPs). Two distinct NK cell subsets were generated in vitro from CD34+CD117+α4β7+Lin-CD48-CD52+ and CD34+CD117+α4β7+Lin-CD48+CD52+ NKPs, respectively. Independent of NKPs, ILCPs exist in the CD34+CD117+α4β7+Lin-CD48+CD52+ subset and give rise to ILC1s, ILC2s and NCR+ ILC3s, whereas CD34+CD117+α4β7+Lin-CD48+CD52- ILCPs give rise to a distinct subset of ILC3s that have lymphoid tissue inducer (LTi)-like properties. Additionally, CD48 expressing CD34+CD117+α4β7+Lin- precursors give rise to tissue-associated ILCs in vivo. We also observed that the interaction of 2B4 with CD48 induced differentiation of ILC2s, and together these findings show that expression of CD48 by human ILCPs modulates ILC differentiation.
2020-11-20 | GSE160009 | 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:Innate lymphoid cells (ILCs) 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 identify ILCP that are present in the blood and all tested lymphoid and non-lymphoid human tissues. Human ILCP fail to express the signature transcription factors (TF) and cytokine outputs of mature NK cells and ILCs but are epigenetically poised to do so. Human ILCP robustly generate all ILC subsets in vitro and in vivo. While human ILCP express RAR related orphan receptor C (RORC), circulating ILCP can be found in RORC-deficient patients that retain potential for EOMES+ NK cells, T-BET+ ILC1, GATA-3+ ILC2 and for IL-22+ but not for IL-17A+ ILC3. We propose a model of tissue ILC differentiation (‘ILC-poiesis’) whereby diverse ILC subsets are generated in situ from ILCP in response to environmental stressors, inflammation and infection.
2017-03-19 | GSE90640 | GEO
Project description:Innate lymphoid cells (ILC) are tissue-resident effector cells with important roles in tissue homeostasis, protective immunity and inflammatory disease. Here we investigated the role of the transcription factor Bcl6 in small intestinal innate lymphoid cells. Specifically, we performed single-cell RNA-seq on total small intestine lamina propria ILCs from tamoxifen-treated Id2-CreERT2 ROSA26-tdRFP Bcl6-fl/fl mice and Id2-CreERT2 ROSA26-tdRFP controls.
2023-10-31 | E-MTAB-12864 | biostudies-arrayexpress