Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Systemic human ILC precursors provide a substrate for tissue ILC differentiation

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE90640 | GEO | 2017/03/19

SECONDARY ACCESSION(S): PRJNA355273

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Glucocorticoids inhibit human hematopoietic stem cell differentiation toward a common ILC precursor

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

Clarification of human blood ILC subtype interrelatedness and discovery of amphiregulin production by human NK cells shed light on HIV-1 pathogenesis

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

Systemic human ILC precursors provide a substrate for tissue ILC differentiation

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

Intestinal ILC progenitors differentially generate ILC subsets dependent on the recipient tissue microenvironment

Project description:Innate lymphoid cells (ILC) are critical in maintaining tissue homeostasis, and during infection and inflammation. Using combinatorial reporter mice we demonstrate the existence of rare, small intestinal lamina propria (siLP)- resident, ILC progenitors (siLP-ILCP) in adult mice. Transfer of siLP-ILCP into recipients generated ILC1/NK cells, ILC2 and ILC3 within the siLP microenvironment, but only ILC1/NK cells in the liver, lung and spleen. Single cell gene expression analysis confirmed the phenotype of the siLP-ILCPs and ILC progeny and indicated that siLP-ILCP-derived ILC1/NK cells from the siLP have a more tissue-resident phenotype than those from the lungs. Thus, in contrast to bone marrow-derived ILCPs, a local pool of siLP-ILCP can contribute to pan-ILC production in the intestinal microenvironment but has restricted potential in other tissues. Therefore, ILCP potential is influenced by both tissue of origin and the microenvironment during development. This may provide additional flexibility during the tuning of immune reactions.

2024-08-01 | GSE234835 | GEO

Human Innate Lymphoid Cell Precursors Express CD48 that Modulates ILC Differentiation through 2B4 Signaling

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

Gene expression profiling of small intestine (SI) NKp46+RORgt+ and NKp46+RORgt- Innate Lymphoid Cells (ILCs)

Project description:The aim of this study was to analyze the global transcriptional profiles of small intestine (SI) Innate Lymphoid Cells (ILCs) expressing the NK cell marker NKp46. Based on differential expression of the RORgt transcription factor SI NKp46+ ILCs can be divided in NKp46+RORgt- and NKp46+RORgt+ cells. While NKp46+RORgt- cells produce IFN-g, like conventional Natural Killer (NK) cells, NKp46+RORgt+ cells secrete IL-22, like Lymphoid Tissue inducer (LTi) cells. We compared the global transcriptional profiles of both NKp46+RORgt- and NKp46+RORgt+ cells to conventional splenic NK cells and to SI NKp46-RORgt+ cells, which contain adult LTi cells. By following this approach, we showed that SI NKp46+RORγt- ILCs correspond to SI NK cells. We also identified a transcriptional program conserved in adult SI NKp46+RORγt+, NKp46-RORγt+ ILCs and fetal LTi. The various ILC cell populations analyzed in this study were isolated from C57BL/6 RORc(gt)+/GFP reporter mice. SI NKp46+RORγt- (NKp46+GFP-) cells, SI NKp46+RORγt+ cells (NKp46+GFPlow and NKp46+GFPhigh cells) and NKp46-RORγt+ ILCs, including adult LTi cells , were sorted by flow cytometry from CD3- lamina propria cells of small intestine (SI) of RORc(γt)+/GFP reporter mice . Splenic NKp46+RORγt- (NKp46+GFP-) cells were also sorted as the reference for conventional NK cells. Two replicates of each populations were produced and analyzed.

2011-06-20 | E-GEOD-29777 | biostudies-arrayexpress

Polychromic reporter mice reveal unappreciated innate lymphoid cell progenitor heterogeneity and elusive ILC3 progenitors in bone marrow

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

Comprehensive protein-expression map of ILC2 and ILC3 subsets in healthy human skin

Project description:Innate lymphoid cells (ILCs) have emerged as essential players in the skin-associated immune system in health and inflammatory skin diseases. Their low numbers and lack of specific markers hampered extensive characterization and consequently resulted in limited knowledge of their protein expression. Here, we combined flow cytometry and state-of-the-art proteomics to comprehensively describe the proteins constitutively expressed by ILC2 and ILC3 subsets derived from healthy human skin and peripheral blood. We quantified 6666 proteins from skin ILC and identified 608 differentially expressed proteins in the investigated subsets. In addition to the current analyses, highlighting new functions of ILC, the ILC proteomic libraries and the proteomes of the ILC2 and ILC3 subsets will serve as valuable resources for future analyses of ILC function and are available at http://skin.science.

2023-10-10 | PXD037817 | Pride

CD45RA+CD62L- ILCs represent a quiescent local reservoir for the generation of mature ILC in human tissues

Project description:Innate lymphoid cells (ILCs) are highly plastic and predominantly mucosal tissue-resident cells that contribute to both homeostasis and inflammation depending on the microenvironment. The recent discovery of naïve-like tissue-resident ILCs suggests an ILC differentiation process that is akin to naïve T cell differentiation. Delineating the naïve-like ILC heterogeneity and the transcriptional, epigenetic and functional mechanisms that underlie ILC differentiation in tissues is crucial for understanding ILC biology in health and disease. Here we show that CD62L distinguishes two subsets of naïve-like CD45RA+ ILCs in tonsil tissue. While both subsets contain uni- and multipotent precursors of ILC1/NK cells and ILC3, CD62L+ ILCs resemble bona fide naïve ILCs with metabolism reminiscent of naïve T cells, lacking transcriptional and epigenetic signatures of mature ILCs. CD62L- ILCs are epigenetically similar to, but transcriptionally distinct from CD62L+ naïve-like ILCs including transcripts of cytokine signaling and metabolic pathways related to mature ILCs. A similar population of CD62L- quiescent ILCs with preferential differentiation capacity towards IL-22-producing ILC3 accumulate in the inflamed mucosa of patients with inflammatory bowel disease (IBD). These data suggest that naïve-like and quiescent ILCs are imprinted by their tissue microenvironment that poises their differentiation potential. Our findings identify restoration of homeostatic IL-22-producing ILC3 from CD62L- quiescent ILCs as a potential approach to improve tissue healing in IBD.

2022-02-17 | GSE176367 | GEO

Dynamic single-cell regulomes characterize human peripheral blood ILC subpopulations [scATAC-seq]

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data