Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mast cell heterogeneity in human nasal polyps

ABSTRACT: Mast cells (MCs) expressing a distinctive protease phenotype (MCTs) selectively expand within the epithelium of human mucosal tissues during type 2 (T2) inflammation. While MCTs are phenotypically distinct from subepithelial MCs (MCTCs), signals driving human MCT differentiation and this subset’s contribution to inflammation remain unexplored. Here, we identify TGF-b as a key driver of the MCT transcriptome in nasal polyps. We find that short-term TGF-b signaling alters MC cell surface receptor expression and partially recapitulates the in vivo MCT transcriptome, while TGF-β signaling during MC differentiation upregulates a larger number of MCT-associated transcripts and inhibits the hallmark MCTC proteases chymase and cathepsin G at both the transcript and protein level, allowing selective in vitro differentiation of MCTs for functional study. We identify discrete differences in effector phenotype between in vitro-derived MCTs and MCTCs, with MCTs greatly enhancing pro-inflammatory lipid mediator generation while selectively modifying cytokine, chemokine, and growth factor production in response to both innate and adaptive stimuli, recapitulating functional features of their tissue-associated counterpart MC subsets. Thus, our findings support a role for TGF-β in promoting human MCT differentiation and identify a discrete contribution of this cell type to T2 inflammation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE279289 | GEO | 2024/11/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

RHINOVIRUS INFECTION OF THE AIRWAY EPITHELIUM ENHANCES MAST CELL IMMUNE RESPONSES VIA EPITHELIAL-DERIVED INTERFERONS

Project description:Rationale: Mast cells (MCs) within the airway epithelium in asthma are closely related to airway dysfunction, but crosstalk between airway epithelial cells (AECs) and MCs in asthma remains incompletely understood. Human rhinovirus (HRV) infections are key triggers for asthma progression and AECs from individuals with asthma may have dysregulated anti-viral responses. Objectives: We utilize primary phenotyped AECs in an ex vivo coculture model system to examine crosstalk between AECs and MCs following epithelial HRV infection. Methods: Primary AECs were obtained from children with asthma (n=11) and healthy children (n=10), differentiated at air-liquid interface, and cultured in the presence of laboratory of allergic diseases-2 (LAD2) MCs. AECs were infected with HRV serogroup A 16 (HRV16) for 48 hours. RNA isolated from both AECs and MCs underwent RNA-sequencing (RNAseq) analysis. Direct effects of epithelial-derived interferons on LAD2 MCs were examined by qPCR. Results: MCs increased expression of pro-inflammatory and anti-viral genes in AECs. AECs demonstrated a robust antiviral response following HRV16 infection that resulted in significant changes in MC gene expression, including upregulation of genes involved in anti-viral responses, leukocyte activation, and type-2 (T2) inflammation. Subsequent ex vivo modeling demonstrated that IFN-β induces MC IL13 expression. The effects of AEC phenotype were small relative to the effects of viral infection and the presence of MCs. Conclusions: There is significant crosstalk between AECs and MCs, which are present in the epithelium in asthma. Epithelial-derived interferons not only play a role in viral suppression, but further alter MC immune responses including specific T2 genes.

2022-06-22 | GSE206680 | GEO

Definitive classification of ovarian mature cystic teratomas origin using B allele frequency plots with SNP array analysis

Project description:Ovarian mature cystic teratomas (MCTs) originate from postmeiotic germ cells, and some are thought to result from the fusion of two ova. The aim of this study was to determine whether this mechanism is in fact involved in MCT development. MCTs can be classified by the zygosity of the centromere and distal chromosome regions. We evaluated the zygosity of all chromosomes from 38 MCT specimens using B allele frequency (BAF) plots of single nucleotide polymorphism-array data. Theoretically, MCTs originated from the fusion of two ova should have a mixed pattern of centromeric zygosity, i.e., a combination of heterozygous and homozygous regions. However, no MCTs in this series met this criterion as evidenced by BAF plots, suggesting that the fusion of two ova is not mechanistically involved in the development of ovarian teratomas. Thus, MCTs were classified into three types originating from meiosis I and meiosis II errors, and endoduplication of a mature ovum. The numbers of recombination events occurring with type I and II MCTs were somewhat higher than in regular oogenesis. In addition, BAF plots could facilitate the construction of recombination maps at the whole-genome level for type I and II MCTs. In conclusion, our findings provide evidence against the hypothesis that MCTs originate from the fusion of two ova and indicate that BAF plots could serve as useful analytical tools for analyzing MCT cytogenetics and human oocyte meiosis.

2018-07-22 | GSE85424 | GEO

Alternative activation of mast cells by CD4+ T helper cells

Project description:Effector CD4+ T lymphocytes (Teff) infiltrate sites of inflammation and orchestrate the immune response by instructing local leukocytes. Mast cells (MCs) are tissue sentinel cells strategically located near blood vessels and T cell rich areas. MC/Teff cells interactions shape Teff cell responses but in turn, Teff cell action on MC is still poorly understood. Here, we analyzed the human MC/Teff cells interplay through the application of RNAseq and functional assays and showed that activated Teff cells induced a specific transcriptomic program in MCs driving them toward an inflammatory phenotype. Teff cells affected key MC immune functions as they induced prostaglandin, inflammatory cytokines and chemokines production and fostered FceRI-dependent degranulation. Moreover, Teff cell induced in MCs the capacity to regulate T cell responses through a wide-range of dedicated soluble and membrane ligands. Cell-Cell communication inference based on transcriptomic data indicated that IFN-g, IL-21, IL-27 and IL-1b were the main driver of MC differentiation program.

2024-07-03 | GSE235240 | GEO

Gene expression data of human peripheral blood-derived cultured mast cells

Project description:Mast cell (MC) activation contributes considerably to immune responses, such as host protection and allergy. Cell surface immunoreceptors expressed on MCs play an important role in MC activation. Although various immunoreceptors on MCs have been identified, the regulatory mechanism of MC activation is not fully understood. To understand the regulatory mechanisms of MC activation, we used gene expression analyses of human MCs to identify a novel immunoreceptor expressed on MCs. We found that Tek, which encodes Tie2, was preferentially expressed in the MCs of humans.

2015-12-21 | GSE71247 | GEO

A novel approach for studying mast cell-driven disorders: mast cells derived from induced pluripotent stem cells

Project description:We developed a novel strategy for the rapid and efficient differentiation of MCs from human induced pluripotent stem cells (hiPSC). These hiPSC-derived MCs (hiPSC-MCs) exhibit phenotypic and functional characteristics of human skin MCs (hsMCs) and peripheral hematopoietic stem cell-derived MCs (PSCMCs). hiPSC-MCs display stable expression of MC-associated receptors such as CD117, FcεRIα and MRGPRX2, and degranulate by stimulation with IgE/anti-IgE and Substance. P.

2022-08-31 | GSE181457 | GEO

IgE antibodies increase honeybee venom responsiveness and detoxification efficiency of mast cells

Project description:In contrast to their clearly defined roles in allergic diseases, the physiologic functions of Immunoglobulin E antibodies (IgEs) and mast cells (MCs) remain enigmatic. Recent research supports the toxin hypothesis, showing that MCs and IgE-related type 2 immune responses can enhance host defense against certain noxious substances, including honeybee venom (BV). However, the mechanisms by which MCs can interfere with BV toxicity are unknown. In this study, we assessed the role of IgE and certain MC products in MC-mediated BV detoxification. We applied in vitro and in vivo fluorescence microscopy imaging, and flow cytometry, fibroblast-based toxicity assays and mass spectrometry to investigate IgE-mediated detoxification of BV cytotoxicity by mouse and human MCs in vitro. Pharmacologic strategies to interfere with MC-derived heparin and proteases helped to define the importance of specific detoxification mechanisms. Venom-specific IgE increased the degranulation and cytokine responses of MCs to BV in vitro. Passive serum sensitization enhanced MC degranulation in vivo. IgE-activated mouse or human MCs exhibited enhanced potential for detoxifying BV by both proteolytic degradation and heparin-related interference with toxicity. Mediators released by IgE-activated human MCs efficiently degraded multiple BV toxins. Our results both reveal that IgE sensitization enhances the MC’s ability to detoxify BV and also assign efficient toxin-neutralizing activity to MC-derived heparin and proteases. Our study thus highlights the potential importance of IgE, MCs, and particular MC products in defense against BV.

2021-11-25 | PXD023851 | Pride

Mast cell cytonemes as a defense mechanism against Coxiella burnetii

Project description:Mast cells (MCs) are critical mediators of inflammation; however, their microbicidal activity against invading pathogens remains largely unknown. Here, we describe a nonpreviously reported antibacterial mechanism used by MCs against Coxiella burnetii, the agent of Q fever. We show that C. burnetii interaction with MCs does not result in bacterial uptake but rather induces the formation of extracellular actin filaments named cytonemes. MC cytonemes express cathelicidin and neutrophil elastase and mediate the capture and destruction of entrapped bacteria. We provide evidence that MC cytoneme formation and microbicidal activity are dependent on the cooperation of the scavenger receptor CD36 and Toll-like receptor 4. Taken together, our results suggest that MCs use an extracellular sophisticated mechanism of defense to eliminate intracellular pathogens, such as C. burnetii, before their entry into host cells.

2019-03-13 | GSE111971 | GEO

Characterization of the novel spontaneously immortalized rat Müller cell line SIRMu-1

Project description:Müller cells (MCs) play a crucial role in the retina, and cultured MC lines are an important tool with which to study MC function. Transformed MC lines have been widely used; however, the transformation process can also lead to unwanted changes compared to the primary cells from which they were derived. A monoclonal spontaneously immortalized rat Müller cell line, SIRMu-1, was derived from primary rat MCs and characterized by RNA-sequencing (in addition to immunofluorescence and western blotting) in comparison to primary MCs and the SV40-immortalized MC line, rMC-1.

2018-12-01 | GSE123161 | GEO

Mast cell intracellular traps (MIT) release neutrophil effector proteins during degranulation and nexocytosis

Project description:Degranulating mast cells (MCs) release inflammatory mediators (proteins, lipids, small molecules), including chemokines and chemoattractants, which recruit other immune cells in tissues. Neutrophils can initiate self-amplifying swarming responses via intercellular communication through the lipid leukotriene B4 (LTB4). Initially discovered by two-photon intravital microscopy in mice and confocal live cell imaging, we show that degranulating MCs release LTB4 and exploit this attractant by re-directing neutrophils to MCs. In a process generally termed entosis, neutrophil cluster formation around MCs results in the trapping of living neutrophils inside MC vacuoles in vivo and in vitro. Thus, we identify a novel cell-in-cell structure between MCs and neutrophils, which we term “Mast Cell Intracellular Trap” (MIT). Compared to MCs, MITs revealed improved MC metabolism and recovery after degranulation. This leads to several benefits for MITs: (1) they can be more efficiently re-stimulated than MCs, (2) they show improved survival under nutrient limitation, and (3) MITs store neutrophil proteins, DNA and effector molecules, which can be released after re-stimulation. In this context, we compare the secretome (secreted proteins) of MCs and MITs (in cell culture) before and subsequent to degranulation via label-free nanoLC-MS. In summary, mast cells trap and cannibalize swarming neutrophils, which supply nutrients, proteins and inflammatory molecules to recovering MCs. Our studies may have potential implications for chronically activated MCs in MC-related immune disorders.

2024-06-18 | PXD044140 | Pride

Mast cell-derived SAMD14 is a novel regulator of the human prostate tumor microenvironment

Project description:Mast cells (MCs) are important cellular components of the tumor microenvironment and are significantly associated with poor patient outcomes in prostate cancer and other solid cancers. The promotion of tumor progression partly involves heterotypic interactions between MCs and cancer-associated fibroblasts (CAFs) which combine to potentiate a pro-tumor extracellular matrix and promote epithelial cell invasion and migration. Thus far, the interactions between MCs and CAFs remains poorly understood. To identify molecular changes that may alter resident MC function in the prostate tumor microenvironment, we profiled the transcriptome of human prostate MCs, isolated from patient-matched non-tumor and tumor-associated regions of fresh radical prostatectomy tissue. Transcriptomic profiling revealed a distinct gene expression profile of MCs isolated from prostate tumor regions, including the downregulation of SAMD14, a putative tumor suppressor gene. Proteomic profiling revealed overexpression of SAMD14 in HMC-1 MCs altered the secretion of proteins associated with immune regulation and extracellular matrix processes. To assess MC biological function within a model of the prostate tumor microenvironment, HMC-1-SAMD14+ conditioned media was added to co-cultures of primary prostatic CAFs and prostate epithelium. HMC-1-SAMD14+ secretions were shown to reduce the deposition and alignment of matrix produced by CAFs and suppress pro-tumorigenic prostate epithelial morphology. Overall, our data presents the first profile of human MCs derived from patient prostate cancer specimens and identifies MC-derived SAMD14 as an important mediator of MC phenotype and function within the prostate tumor microenvironment.

2021-03-12 | PXD022782 | Pride

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