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Cyclic hypoxia induces transcriptomic changes in mast cells leading to a hyperresponsive phenotype after FcεRI crosslinking

ABSTRACT: Cyclic hypoxia induces transcriptomic changes in mast cells leading to a hyperresponsive phenotype after FcεRI crosslinking

PROVIDER: PRJNA833125 | ENA |

REPOSITORIES: ENA

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Cyclic hypoxia induces transcriptomic changes in mast cells leading to a hyperresponsive phenotype after FcεRI crosslinking

Project description:Mast cells (MCs) play an important role in tumor development, executing pro or antitumoral functions depending on tumor type and local conditions present in the tumor microenvironment such as cyclic hypoxia (cyH), which is a distinguishing feature of almost all solid tumors. In this study, we analyzed transcriptional changes of murine bone marrow-derived mast cells (BMMCs) exposed to an in vitro protocol of cyH, consisting of interleaved cycles of hypoxia and re-oxygenation at 1% and 21% of oxygen, respectively. Utilizing a mouse M22K microarray (Microarray Unit, Cellular Physiology Institute, UNAM, Mexico City), we identified 2512 genes in MCs subjected to cyH whose expression displayed changes compared with normoxic cells. Furthermore, functional enrichment analysis revealed that cyH-related transcriptomic alterations were for genes associated with oxidative phosphorylation and the FcεRI signaling pathway. Interestingly, after IgE/ antigen (Ag) challenge, FcεRI-dependent degranulation, calcium mobilization, and PLC-γ activity were enhanced in BMMCs exposed to cyH compared to those cells maintained in normoxic conditions. In addition, the expression of calcium signaling-related cytokines such as TNF-α, IL-4, and IL-2 was increased in BMMCs exposed to cyH after IgE/Ag challenge. Taken together, these findings indicate that cyH induces transcriptomic modifications in MCs that are translated into a phenotypic change characterized by hyperresponsiveness to IgE/Ag challenge.

2022-05-01 | GSE201828 | GEO

Transcription profiling of human umbilical cord blood derived mast cells IgE sensitized followed by crosslinking receptor at different time points

Project description:Human umbilical cord blood derived mast cells IgE sensitized followed by crosslinking receptor at different time points

2008-06-11 | E-GEOD-1933 | biostudies-arrayexpress

Cyclic Hypoxia Induces Transcriptomic Changes in Mast Cells Leading to a Hyperresponsive Phenotype after FcεRI Cross-Linking.

Project description:Mast cells (MCs) play important roles in tumor development, executing pro- or antitumoral functions depending on tumor type and tumor microenvironment (TME) conditions. Cyclic hypoxia (cyH) is a common feature of TME since tumor blood vessels fail to provide a continuous supply of oxygen to the tumor mass. Here, we hypothesized that the localization of MCs in cyH regions within solid tumors could modify their transcriptional profile and activation parameters. Using confocal microscopy, we found an important number of MCs in cyH zones of murine melanoma B16-F1 tumors. Applying microarray analysis to examine the transcriptome of murine bone-marrow-derived MCs (BMMCs) exposed to interleaved cycles of hypoxia and re-oxygenation, we identified altered expression of 2512 genes. Functional enrichment analysis revealed that the transcriptional signature of MCs exposed to cyH is associated with oxidative phosphorylation and the FcεRI signaling pathway. Interestingly, FcεRI-dependent degranulation, calcium mobilization, and PLC-γ activity, as well as Tnf-α, Il-4, and Il-2 gene expression after IgE/antigen challenge were increased in BMMCs exposed to cyH compared with those maintained in normoxia. Taken together, our findings indicate that cyH causes an important phenotypic change in MCs that should be considered in the design of inflammation-targeted therapies to control tumor growth.

| S-EPMC9319477 | biostudies-literature

Mast Cell_time series

Project description:Human umbilical cord blood derived mast cells IgE sensitized followed by crosslinking receptor at different time points Keywords: time-course

2006-08-21 | GSE1933 | GEO

Transcriptional heterogeneity of mast cells and basophils upon activation. [mast cells]

Project description:We performed large-scale comparative microarrays of bone marrow -derived mast cells and basophils at rest, upon an adaptive-type action (IgE-crosslinking) or upon innate-type activation (IL-33-activation).

2017-03-17 | GSE96695 | GEO

Transcriptomic profiling of human CD34+ derived mast cells [RNA-Seq]

Project description:Transcriptome of human mast cells is extensively reorganized upon FcεRI crosslinking

2019-12-01 | GSE107316 | GEO

Epigenetic profiling of human CD34+ derived mast cells [ChIP-Seq]

Project description:The chromatin landscape of human mast cells is extensively reorganized upon FcεRI crosslinking

2019-12-01 | GSE107315 | GEO

Stem cell factor programs the mast cell activation phenotype

Project description:Mast cells, activated by antigen via the high affinity receptor for IgE (FcεRI), release an array of pro-inflammatory mediators that contribute to allergic disorders such as asthma and anaphylaxis. The KIT ligand, stem cell factor (SCF), is critical for mast cell expansion, differentiation and survival, and, under acute conditions, enhances mast cell activation. However, extended SCF exposure in vivo conversely protects against fatal antigen-mediated anaphylaxis. In investigating this dichotomy, we identified a novel mode of regulation of the mast cell activation phenotype through SCF-mediated programming. We found that mouse bone marrow-derived mast cells chronically exposed to SCF displayed a marked attenuation of FcεRI-mediated degranulation and cytokine production. The hypo-responsive phenotype was not a consequence of altered signals regulating calcium flux or protein kinase C, but of ineffective cytoskeletal reorganization, with evidence implicating a down-regulation of expression of the Src kinase Hck. Collectively, these findings demonstrate a major role for SCF in the homeostatic control of mast cell activation with potential relevance to mast cell-driven disease and the development of novel approaches for the treatment of allergic disorders. Mouse bone marrow-derived mast cells were treated with IL3, IL3+IL33, or IL3+SCF. Six replicates each.

2012-05-01 | E-GEOD-35332 | biostudies-arrayexpress

Transcriptional heterogeneity of mast cells and basophils upon activation. [basophils]

2017-03-17 | GSE96694 | GEO

Stem cell factor programs the mast cell activation phenotype

2012-05-02 | GSE35332 | GEO