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Immune cell infiltration into brain tumor microenvironment is mediated by Rab27-regulated vascular wall integrity

ABSTRACT: Immune cell infiltration into brain tumor microenvironment is mediated by Rab27-regulated vascular wall integrity

PROVIDER: PRJNA1118199 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29234105_1.fastq.gz	Fastqsanger.gz
	SRR29234105_2.fastq.gz	Fastqsanger.gz
	SRR29234106_1.fastq.gz	Fastqsanger.gz
	SRR29234106_2.fastq.gz	Fastqsanger.gz
	SRR29234107_1.fastq.gz	Fastqsanger.gz

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Immune cell infiltration into brain tumor microenvironment is mediated by Rab27-regulated vascular wall integrity

Project description:Aggressive brain tumors often exhibit immunologically ‘cold’ microenvironment, where the vascular barrier impedes effective immunotherapy in poorly understood ways. Tumor vasculature also plays a pivotal role in immunoregulation and antitumor immunity. Here we show that small GTPase Rab27 controls the vascular morphogenesis and permeability for blood content and immune effectors. Thus, in Rab27a/b double knock out (Rab27-dKO) mice, the brain vasculature is abnormally scarce while the blood vessels become dysmorphic and hyperpermeable in the context of brain tumors, including syngeneic glioblastoma. These defects are reflected in rearrangements of endothelial cell subpopulations with underlying diminution of venous endothelial subtype along with changes in gene and protein expression. Notably, Rab27-dKO brain endothelial cells exhibit deficient tight junctions, whereby they enable large-scale extravasation of cytotoxic T cells into the tumor mass. We show that Rab27-regulated vascular T cell infiltration can be exploited to enhance adoptive T cell therapy in syngeneic brain tumors.

2025-06-02 | PXD062939 | Pride

Immune cell infiltration into brain tumor microenvironment is mediated by Rab27-regulated vascular wall integrity

Project description:To investigate the functional role of Rab27a/b in glioblastoma. We established different roles of brain endothelial cells at physoilogical and in tumor states in the genetically mutated Rab27a/b double knock out murine tissues. We performed single cells gene expression profiling analysis using data obtained from RNA-seq from the brains of non-tumor and glioma tissues derived by injection of GL261 tumor cells in Rab27a/b dHET and Rab27a/b dKO mice.

2025-04-15 | GSE268654 | GEO

A seven-membered cell wall related transglycosylase gene family in Aspergillus niger is relevant for cell wall integrity in cell wall mutants with reduced α-glucan or galactomannan

Project description:Chitin is an important fungal cell wall component that is cross-linked to β-glucan for structural integrity. Acquisition of chitin to glucan cross-links has previously been shown to be performed by transglycosylation enzymes in S. cerevisiae, called Congo Red hypersensitive (Crh) enzymes. Here, we characterized the impact of deleting all seven gene members of the crh gene family (crhA-G) in Aspergillus niger on cell wall integrity, cell wall composition and genome-wide gene expression. In this study, we show that the seven-fold knockout strain shows slightly compact plate growth, but no increased sensitivity to cell wall perturbing compounds. Additionally, we found that the cell wall composition of this knockout strain was virtually identical to that of the wild type. In congruence with these data, genome-wide expression analysis revealed very limited changes in gene expression and no signs of activation of the cell wall integrity response pathway. However, deleting the entire crh gene family in cell wall mutants that are deficient in either galactofuranose (ΔugmA) or α-glucan (ΔagsE and ΔagsA, ΔagsE), resulted in a synthetic growth defect and an increased sensitivity towards Congo Red compared the parental strains. Altogether, these results indicate that loss of the crh gene family in A. niger does not trigger the cell wall integrity response in itself, but does play an important role in ensuring cell wall integrity in mutant strains with reduced galactofuranose or α-glucan.

2019-12-21 | GSE142461 | GEO

PARP15 promotes vascular barrier integrity in inflammation

Project description:PARP15 promotes vascular barrier integrity in inflammation

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Active repression of Sox9 by Jag1 is required for silencing the default chondrogenic fate of the vascular smooth muscle wall [set 1]

Project description:Acquisition and maintenance of vascular smooth muscle fate is essential for the morphogenesis and function of the circulatory system. Loss of contractile properties or changes in the identity of vascular smooth muscle cells (vSMC) can result in structural alterations associated with aneurysms and vascular wall calcifications. Here we report that maturation of sclerotome-derived vSMC is dependent on a transcriptional switch between mouse embryonic days 13 and 14.5. At this time point, Jag1-mediated repression of sclerotome transcription factors Pax1, scleraxis and Sox9 is necessary to fully enable vSMC maturation. Specifically, Notch signaling in vSMC antagonizes sclerotome and cartilage transcription factors, and promotes upregulation of contractile genes. In the absence of Jag1, vSMC acquire a chondrocytic transcriptional repertoire that can lead to ossification of the vascular wall. Importantly, our findings suggest that sustained Notch signaling is essential throughout vSMC life to maintain contractile function, prevent vSMC reprogramming and promote vascular wall integrity.

2015-03-23 | GSE60641 | GEO

Active repression of Sox9 by Jag1 is required for silencing the default chondrogenic fate of the vascular smooth muscle wall [set 2]

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An Omics approach on Marchantia polymorpha single FERONIA and MARIS homologs confirms links between cell wall integrity and abscisic acid

Project description:Plant cells are surrounded by an extracellular cell wall that shields them from their abiotic and biotic environment. To coordinate their growth with their cell wall status, they have developed cell wall integrity mechanisms at the center of which lies the transmembrane Malectin-like receptor kinase FERONIA (FER). FER controls a myriad of plant developmental processes including sexual reproduction, cell growth and morphogenesis, often intersecting with phytohormones-dependent pathways such as abscisic acid (ABA) or plant immunity. Interestingly, FER and its downstream receptor-like cytoplasmic kinase MARIS (MRI) were shown to cooperate similarly in the control of root hair and rhizoid integrity for the vascular model Arabidopsis and the early diverging bryophyte model Marchantia polymorpha, respectively. Here, we carried out comparative transcriptomics and proteomics approach on Mpfer-1 and Mpmri-1 knock-down mutant plants and the wild-type strains Tak-1 and Tak-2. Our -omics analyses revealed that globally, MpFER and MpMRI largely cooperate to negatively regulate transcriptional and translational networks in particular those related to plant defense and ABA responses. Moreover, Mpfer-1 plants were found to be hypersensitive to ABA-dependent growth inhibition indicating that FER’s function of negatively regulating ABA-related growth responses is conserved between bryophytes and vascular plants.

2024-11-26 | GSE282327 | GEO

Vascular integrity is essential for maintaining tissue homeostasis

Project description:Vascular integrity is essential for maintaining tissue homeostasis

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TRAF7 is an essential regulator of vascular integrity

Project description:TRAF7 is an essential regulator of vascular integrity

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Vascular integrity is essential for maintaining tissue homeostasis

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