Multiplexed single cell RNA sequencing (scRNA-seq) of ILC3s after various stimulation ex vivo.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE312380 | GEO | 2026/09/09
REPOSITORIES: GEO
Similar Datasets
Project description:Multiplexed single cell RNA sequencing (scRNA-seq) of ILC3s after various stimulation ex vivo.
| PRJNA1373213 | ENA
Project description:Innate lymphoid cells (ILCs) are tissue-resident lymphocytes subdivided into ILC1s, ILC2s and ILC3s based on core regulatory programs and signature cytokines secreted. ILCs exhibit functional plasticity: for instance, human IL-22-producing ILC3s convert into IFN-γ-producing ILC1-like in vitro. Whether this conversion occurs in vivo is unclear. Using flow cytometry, mass cytometry and scRNAseq, here we found that ILC3s and ILC1s occupy opposite ends of a spectrum including discrete subsets in human tonsils. RNA velocity suggested strong directionality toward ILC1s for one ILC3-ILC1 intermediate cluster. Clonal analysis revealed graded ability of ILC3-ILC1 subsets to convert into ILC1-like cells. When examined in humanized mice, ILC3 acquisition of ILC1 features showed tissue-dependency. In chromatin studies, Aiolos emerged as a nuclear factor that cooperates with Tbet to repress evolutionarily conserved regulatory elements active in ILC3s. The human intestine also exhibited an ILC3–ILC1 transitional population. We conclude that conversion of ILC3s to ILC1-like occurs in vivo in human tissues, and that tissue factors and Aiolos are crucial for this process.
2019-06-18 | GSE132843 | GEO
Project description:ILC3s from the spleen (SP) and small intestine (SI) have been shown to be phenotypically and functional different. Intestinal factors are likely to regulate transcriptional profiles and thereby function of ILC3s. The goal of this study is to analyze if SI ILC3s acquire a SP-similar transcriptional profile after in vitro culture. Therefore transcriptional profiles of cultured SI ILC3s were compared to freshly isolated ILC3s of the murine SP and the SI by RNA seq technology. Cell suspension were generated from both organs and ILC3s (CD117+, Thy1.2+, KLRG1-, lin- (CD3, CD8, CD11b, CD11c, CD19, B220, Gr-1, TCRβ, TCRγδ, TER-119, NK1.1)) were sort purified. SI ILC3 were cultured for 7 days in vitro with IL-2, IL-7 and SCF. RNA was isolated and RNA sequencing was done using Ilumina Hiseq 2500 system and NuGEN Ovation RNA Seq System V2, with biological replicates. We show that intestinal ILC3 acquire a splenic-similar transcriptional profile after in vitro culture.
2020-03-17 | GSE114750 | GEO
Project description:GATA3 is indispensable for the development of all IL-7Rα-expressing innate lymphoid cells (ILCs) and maintenance of type 1 ILCs (ILC1s) and type 2 ILCs (ILC2s). However, the importance of low GATA3 expression in type 3 ILCs (ILC3s) is still elusive. Here, we report that GATA3 regulates homeostasis of ILC3s by controlling IL-7Rα expression. In addition, GATA3 is critical for the development of NKp46+ ILC3 subset partially through regulating the balance between T-bet and RORγt. Genome-wide analyses indicate that while GATA3 positively regulates CCR6+ and NKp46+ ILC3 subset-specific genes in respective lineages, it negatively regulates CCR6+ ILC3-specific genes in NKp46+ ILC3s. Furthermore, GATA3 regulates IL-22 production in both CCR6+ and NKp46+ ILC3s. Thus, low GATA3 expression is critical for the development and function of ILC3 subsets. To identify GATA3 regulated genes in total ILC3s with RNA-Seq; To identify unique genes expressed by CCR6+ ILC3 or NKp46+ ILC3 and GATA3 regulated genes within these two ILC3 subsets with RNA-Seq; To identify GATA3 direct binding sites in ILC3s, ILC2s and Th2 cells with ChIP-Seq.
2015-11-23 | E-GEOD-71198 | biostudies-arrayexpress
Project description:To explore the role of circRNAs during ILC3-driven colitis, we isolated ILC3s from DSS treated or control Rag1-/- mice. Then circRNA microArray analysis were performed and differentially expressed circRNAs were identified.
2019-12-17 | GSE142106 | GEO
Project description:Group 3 innate lymphoid cells (ILC3s) are critical regulators of intestinal homeostasis, yet their role in cancer remains elusive. Here, we identify that the tumor microenvironment of humans and mice with colorectal cancer (CRC) contains altered ILC3 responses that resemble those found during intestinal inflammation and are characterized by reduced frequencies, altered subset distribution, and an imbalance with T cells. We evaluated the consequences of these changes in mice and determined that ILC3-specific major histocompatibility complex class II (MHCII) was required to limit the progression of CRC. Interestingly, ILC3-specific MHCII also prevented resistance to anti-PD-1 immunotherapy by regulating intestinal inflammation and microbiota composition. Finally, humans with intestinal inflammation and dysregulated ILC3s also harbor specific microbiota that are sufficient to promote immunotherapy resistance in mice. Collectively, these data define a protective role for antigen-presenting ILC3s in cancer, and indicate that inherent disruption of this pathway drives CRC progression and immunotherapy resistance.
2021-07-09 | GSE165814 | GEO
Project description:Clostridioides difficile infection (CDI) is a common cause of antibiotic-associated colitis. C. difficile proliferates and produces toxins that damage the colonic epithelium, leading to symptoms ranging from mild diarrhea to severe pseudomembranous colitis. The host's innate response to CDI occurs in two phases: an early phase in which neutrophils reduce the bacterial load, and a late phase involving repair mechanisms to restore epithelial integrity. Group 3 innate lymphoid cells (ILC3s) are crucial in protecting the gut from CDI. Previous studies have shown that ILC3 production of IL-22 is essential in the late phase of CDI for epithelial repair and maintaining an intestinal microbiota that competes with C. difficile, preventing its expansion. Our study finds that ILC3s also protect during the early stages of CDI by sustaining neutrophils through GM-CSF. Less neutrophil production, accumulation and activation was evident in ILC3-deficient mice than in wild-type (WT) mice, which led to exacerbated symptoms, impaired pathogen clearance, a compromised epithelial barrier, and increased mortality. The adoptive transfer of ILC3s into ILC3-deficient mice restored neutrophil responses and improved disease outcomes. Both in vitro and in vivo experiments revealed that GM-CSF production by ILC3s is crucial for neutrophil production and effective resistance during CDI. Using mice lacking NKp46+ ILC3s, we found that this subset significantly contributes to GM-CSF production in CDI. These findings highlight the critical role of the ILC3-neutrophil connection in early innate responses to CDI. Enhancing ILC3 production of GM-CSF could be a promising strategy for improving host defense against CDI and other enteric infections.
2024-10-17 | GSE277716 | GEO
Project description:Group 3 innate lymphoid cells (ILC3s) are abundant in the developing or healthy intestine to critically support tissue homeostasis in response to microbial cues and other environmental signals. However, during gastrointestinal disease including infections, colorectal cancer, or inflammatory bowel disease (IBD), intestinal ILC3 numbers are dramatically reduced and the remaining ILC3s become dysfunctional which fuels disease and barrier breakdown. To define the underlying transcriptomic changes, we employed RNA sequencing of ILC3s from IBD patients. This may help to gain a deeper understanding of the mechanisms driving these alterations and ultimately lead to novel preventive, diagnostic, or therapeutic opportunities in IBD.
2024-04-23 | GSE247742 | GEO
Project description:Innate lymphoid cells (ILCs) are long-lived tissue-resident analogues to T helper cell subsets that lack antigen-specific receptors. Understanding the roles of specific ILC subsets in chronic inflammation and fibrosis has been hampered by a lack of adequate tools for their selective targeting. Here, we used two Cre-deleter strains, Il17rb-CreERT2-eGFP and Rorc-Cre, to selectively delete RORa, a master transcriptional regulator, in ILC2s and ILC3/Th17 cells, respectively. Deletion of RORa in ILC2s led to a significant loss of gastrointestinal ILC2s, a concomitant increase in ILC3s, elevated Th17-type responses, and heightened susceptibility to Crohn’s-like fibrosis in a Salmonella infection model. In contrast, RORa deletion in ILC3/Th17 cells reduced IL-17 production, protecting against fibrosis. We further confirmed the role of IL-17 and ILC3 in fibrotic responses using isolithocholic acid (isoLCA), a microbially-derived secondary bile acid and RORγt inverse agonist. In RORγt reporter and Th17-deficient Rag1−/− mice, isoLCA reduced IL-17 production by ILC3s. In the context of intestinal fibrosis, we show that isoLCA attenuates collagen deposition and fibrotic pathology by dampening RORγt-dependent IL-17 production by ILC3s. These findings reveal a novel interplay between ILC2s and ILC3s in gut homeostasis and demonstrate the therapeutic potential of targeting RORγt in ILC3s as a strategy for preventing fibrosis.
2025-05-15 | GSE290467 | GEO
Project description:To investigate the role of IRF4 in the regulation of ILC3 development and function, we used the wildtype mice as control and carried out single-cell RNA sequencing (BD Rhapsody) on gut ILC3s.
2025-06-09 | GSE281331 | GEO