Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transdifferentiation of tumor infiltrating innate lymphoid cells during progression of colorectal cancer

ABSTRACT: Innate lymphoid cells (ILCs) reside in mucosal surfaces to potentiate immune responses, sustain mucosal integrity and maintain tissue homeostasis. However, how tumor infiltrating ILCs modulate tumor development and progression is unclear. Here we profiled tumor infiltrating ILCs during colorectal cancer (CRC) progression by single-cell RNA sequencing. We identified six clusters of tumor infiltrating ILCs with unique features. ILC1s expressed inhibitory receptors and underwent inhibitory functional conversion at the late stage of CRC. ILC2s were classified into three subsets (called ILC2-A, -B, -C), ILC2-C subset could facilitate tumor progression. HS3ST1 and PD1 were highly expressed in ILC2s of late stage CRC tumors and deficiency of HS3ST1 or PD1 in ILC2s suppressed tumor growth. Moreover, ILC3s transdifferentiated into ILCregs during CRC progression and ILCregs promoted tumor growth. Of note, TGF- signaling initiated the conversion of ILC3s to ILCregs and blockade of TGF- signaling could disrupt the ILCreg transdifferentiation and inhibited tumor growth as well. Thus intervention of ILC conversions might be a potential strategy for CRC immunotherapy.

ORGANISM(S): Mus musculus

PROVIDER: GSE142694 | GEO | 2019/12/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription factor Bcl11b controls identity and function of mature innate lymphoid cells type II

Project description:Type-2 innate lymphoid cells (ILC2s) promote anti-helminth responses and contribute to allergies. Though Bcl11b has been previously considered a T-lineage identity transcription factor (TF) that restrains the innate-cell genetic programs, we report here that Bcl11b is highly expressed in mature ILC2s and acts upstream of the key ILC2 TFs Gfi1, Gata-3, and of IL-33 receptor IL1rl1 (T1ST2). Additionally, Bcl11b-/- ILC2s de-repressed Rorγt, Ahr and IL-23 receptor, normally expressed in type-3 ILCs (ILC3s). Consequently, Bcl11b-/- ILC2s lost ILC2 functions and gained ILC3 functions, expanding in response to the protease allergen papain, however producing IL-17 and IL-22, and not IL-5 and IL-13, causing lung neutrophilia rather than eosinophilia, and diminished mucus production. Our results broaden Bcl11b's role from a T-cell only TF, and establishes that Bcl11b sustains mature ILC2 genetic and functional programs and lineage fidelity through positive regulation of essential ILC2 TFs and negative regulation of pivotal ILC3 TFs. RNA-seq analysis on sorted ILC2s from the mLNs of Bcl11bF/F Cre-ERT2 and wildtype mice at steady state following tamoxifen mediated deletion of Bcl11b

2015-07-28 | E-GEOD-67437 | biostudies-arrayexpress

Group 3 innate lymphoid cells continuously require the transcription factor GATA3 after commitment

Project description:GATA3 is indispensable for the development of all IL-7RÎ±-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-7RÎ± expression. In addition, GATA3 is critical for the development of NKp46+ ILC3 subset partially through regulating the balance between T-bet and RORÎ³t. 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

Neuromedin U receptor-1 amplifies inflammatory lung innate lymphoid cells

Project description:Type 2 innate lymphoid cells (ILC2s) promote mucosal homeostasis, yet also contribute to pathologic type 2 inflammation in allergic asthma. Alarmin cytokines produced by damaged and stressed epithelial cells, such as IL-25, activate ILC2s, but it remains unclear if these cytokines are unique in switching homeostatic ILC2s into pro-inflammatory cells that drive tissue inflammation. To identify molecular cues that modulate ILC responses to alarmins, we collected single-cell RNA-seq profiles of lung-resident ILCs at steady state and after in vivo stimulation. Computational and functional analysis identified that ILC2s express the neuropeptide receptor Nmur1. Neuromedin U (NMU), the ligand of Nmur1, activates ILCs in vitro, and when co-administered with IL-25 in vivo, NMU dramatically amplifies allergic inflammation and induces ILC2 expansion. Finally, loss of NMU/Nmur1-signaling reduces ILC2 frequency and effector function following allergen challenge in vivo. Our results demonstrate that Nmur1 signaling modifies alarmin-mediated ILC2 responses to promote pro-inflammatory ILCs, and highlights the importance of neuro-immune crosstalk in allergic inflammatory responses at mucosal surfaces.

2017-09-17 | GSE102299 | GEO

Transcription factor Bcl11b controls identity and function of mature innate lymphoid cells type II

2015-07-28 | GSE67437 | GEO

Group 3 innate lymphoid cells continuously require the transcription factor GATA3 after commitment

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.

2015-11-23 | GSE71198 | GEO

Bone marrow progenitors and IL-2 signaling contribute to the strain differences of kidney innate lymphoid cells

Project description:Innate lymphoid cells (ILCs) are critical mediators of immune responses by their robust production of cytokines. ILCs are mainly present in mucosal tissues, but their regulatory function in the kidney is attracting attention. Nevertheless, the understanding of their unique biology, compared to other tissues, is largely unknown.Here, we aimed to examine the effect of BALB/c and C57BL/6 strains on the number and function of kidney ILCs and their underlying mechanisms. Although the BALB/c strain showed an increase in ILC2 frequency than that of C57BL/6 in most organs, the difference in ILC2 frequency between the two strains was most pronounced in the kidney. These results were derived from increased ILC precursors in the bone marrow, and levels of renal Il2 in BALB/c mice. Furthermore, IL-2 receptor (CD25) expression and STAT5 phosphorylation also exaggerated in BALB/c kidney ILC2s. However, similar IL-2-dependent proliferation and activation of ILC2s were observed upon IL-2C treatment in both strains. Thus, homeostatic differences in kidney ILC2 number and function derive from differences in IL-2 signaling resulting from intrinsic and extrinsic factors. Together, we demonstrate previously unknown properties of kidney ILC2s based on their mice strain background and contributing factors. All these factors should be considered critical for the successful translation of immune diseases in experimental mouse models.

2023-01-31 | GSE208404 | GEO

RNA-seq analysis of the Innate Lymphoid Cells type 2 (ILC2) or their precursors (ILC2p ) sorted from WT and Tgfbr2-/- mice

Project description:Purpose: The molecular pathways underlying the development of innate lymphoid cells (ILCs) are mostly unknown. Results: TGF-β signaling programs the development of ILC2s from their progenitors. Specifically, the deficiency of TGF-β receptor II in bone marrow progenitors results in inefficient development of ILC2s, but not ILC1s or ILC3s. We found that hundreds of genes were changed in Tgfbr2-/- ILC2s compared to WT ILC2s (FDR < 0.1 and Fold-Change >1.5). Some ILC2-associated genes including Gata3, Il1rl1 (ST2), Il-5, Atxn1 (Sca1), and Ccr4 were decreased in Tgfbr2-/- ILC2s, according to RNA-seq analysis Conclusions: TGF-β upregulates the expression of the IL-33 receptor gene Il1rl1 (encoding IL-1 receptor-like 1, also known as ST2) in ILC2p and common helper-like innate lymphoid progenitors (CHILP), at least partially through the MEK-dependent pathway. These findings identify a function of TGF-β in the development of ILC2s from their progenitors.

2019-11-09 | GSE140168 | GEO

Identification of human cytotoxic ILC3s

Project description:Human ILCs are classically categorized into five subsets; cytotoxic CD127-CD94+ NK cells and non-cytotoxic CD127+CD94-, ILC1s, ILC2s, ILC3s and LTi cells. Here, we identify a novel subset within the CD127+ ILC population, characterized by the expression of the cytotoxic marker CD94. These CD94+ ILCs strongly resemble conventional ILC3s in terms of phenotype, transcriptome and cytokine production, but are highly cytotoxic. IL-15 was unable to induce differentiation of CD94+ ILCs towards mature NK cells. Instead, CD94+ ILCs retained RORγt, CD127 and CD200R expression and produced IL-22 in response to IL-15. Culturing non-cytotoxic CD127+ ILC1s or ILC3s with IL-12 induced upregulation of CD94 and cytotoxic activity, effects that were not observed with IL-15 stimulation. Thus, human helper ILCs can acquire a cytotoxic program without differentiating into NK cells.

2020-09-14 | GSE147231 | GEO

Group 3 innate lymphoid cells mediate early protective immunity against Mycobacterium tuberculosis

Project description:We report the phenotype of human lung ILC2 and ILC3 populations from individuals with tuberculosis (TB) and non-TB cancer controls. We find that ILC2s demonstrate moderate transcriptional differences in TB infection, whereas ILC3s demonstrate large differences.

2019-05-11 | GSE131031 | GEO

Intermediate GATA3 expression renders a noncanonical ILC population in skin essential for hair follicle recycling

Project description:We find that the expression of GATA3 in skin ILCs is significantly lower than in conventional ILC2s of other tissues, indicating that the regulatory role of GATA3 may be different. Indeed, skin ILCs are still maintained after inducing Gata3 depletion in Gata3fl/flCreERT2 mice, when all ILC2s were gone. In addition, about 70% skin ILCs are found to experience RORγt expression as reflected by RORγt fate-mapping. And, conditional Gata3 depletion in the RORγt fate-mapped skin ILCs does not affect their number as well. Therefore, in contrast to conventional ILC2s, GATA3 is not required for skin ILCs for their maintenance. The RORγt fate-mapped skin ILCs have exhibited ILC3-like features. Single-cell transcriptome analysis further reveals that skin ILCs converge on a Ccr6+ ILC3-like state and an Il1rl1+ ILC2-like state. The regulatory role of GATA3 is crucial in the ILC3-like skin ILCs. It promotes the expression of their featured genes, while suppresses the expression of ILC2-like skin ILC featured genes. These ILC3-like skin ILCs locate in close proximity to hair follicles. During hair follicle recycling they migrate from isthmus to suprabulbar to promote the hair follicle growth. Whereas in absence of Gata3, the ILC3-like skin ILCs exhibit defective migration to the suprabulbar and reduced expression of the featured genes in this process. Together, our study evidence that skin ILCs are alternative to conventional ILC2s. In particular, we shed light on the function of GATA3 in promoting the specific gene expression in ILC3-like skin ILCs and regulating their crucial roles in hair follicle recycling, which will improve our knowledge about the involvement of ILCs in maintaining homeostasis of skin.

2022-02-05 | GSE195973 | 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