Choroid plexus mast cells drive tumor-associated hydrocephalus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA856132 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Tumor-associated hydrocephalus (TAH) is a common and lethal complication of brain metastases. Although other factors beyond mechanical obstructions have been suggested, the exact mechanisms are unknown. Using single-nucleus RNA-sequencing and spatial transcriptomics, we find that a distinct population of mast cells locate in the choroid plexus and dramatically increase during TAH. Genetic fate-tracing and intracranial mast cell-specific tryptase knockout showed that choroid plexus mast cells (CPMCs) disrupt cilia of choroid plexus epithelia via the tryptase-PAR2-FoxJ1 pathway and consequently increase cerebrospinal fluid production. Mast cells are also found in the human choroid plexus. Levels of tryptase in cerebrospinal fluid are closely associated with clinical severity of TAH. BMS-262084, an inhibitor of tryptase, can cross blood-brain-barrier, inhibits TAH in vivo and alleviates mast cell-induced damage of epithelial cilia in a human pluripotent stem cell-derived choroid plexus organoid model. Collectively, we uncover the function of CPMCs and provide an attractive therapy for TAH.
2023-11-22 | GSE207546 | GEO
Project description:Add1 Null mice on the C57BL/6J background develop hydrocephalus that may be due to gene expression changes in the choroid plexus. We used microarrays to detail choroid plexi gene expression prior to the manifestation of hydrocephalus. Choroid plexi from the four ventricle were dissected out, for RNA extraction and hybridization to Affymetrix microarrays, from male Add1 wildtype, heterozygous and null mice at three weeks of age. Five mice were selected for each genotype to assess gene expression prior to the development of hydrocephalus.
2012-04-08 | E-GEOD-37098 | biostudies-arrayexpress
Project description:Add1 Null mice on the C57BL/6J background develop hydrocephalus that may be due to gene expression changes in the choroid plexus. We used microarrays to detail choroid plexi gene expression prior to the manifestation of hydrocephalus.
2012-04-09 | GSE37098 | GEO
Project description:Atoh1-Cre; Myc/Myc mice developed choroid plexus papilloma and Atoh1-Cre; Myc/Myc; p53fl/fl mice developed choroid plexus carcinoma. By studying the gene expression profiles of normal choroid plexus, choroid plexus papilloma and choroid plexus carcinoma in mice, we aim to gain a better understanding of the biology of choroid plexus tumors
2019-05-01 | GSE126327 | GEO
Project description:Integrated multi-omics investigation of novel rat models of acquired hydrocephalus, Blood or bacteria in CSF trigger similar choroid plexus (ChP) immune-secretory responses, Crosstalk between ChP immune and epithelial cells drives CSF hypersecretion and ventriculomegaly, Repurposed systemic immunomodulators ameliorate acquired hydrocephalus, Identification of a druggable hub of ChP function relevant for multiple neurological diseases.
2023-02-17 | GSE192946 | GEO
Project description:Integrated multi-omics investigation of novel rat models of acquired hydrocephalus, Blood or bacteria in CSF trigger similar choroid plexus (ChP) immune-secretory responses, Crosstalk between ChP immune and epithelial cells drives CSF hypersecretion and ventriculomegaly, Repurposed systemic immunomodulators ameliorate acquired hydrocephalus, Identification of a druggable hub of ChP function relevant for multiple neurological diseases.
2023-02-17 | GSE218143 | GEO
Project description:Gene expression profiles generated from human tumor cells laser-microdissected from surgical samples of seven choroid plexus papillomas (Grade I WHO) as eight samples of epithelial cells lasermicrodissected from normal choroid plexus obtained at autopsy. Choroid plexus tumors are rare pediatric brain tumors derrived from the choroid plexus epithelium. Gene expression profiles of lasermicrodissected tumor cells from 7 individual choroid plexus tumor samples obtained at surgery were compared to gene expression profiles from non-neoplastic choroid plexus epithelial cells lasermicrodissected from normal non-neoplastic choroid plexus obtained at autopsy (Am J Surg Pathol. 2006 Jan;30(1):66-74.) in order to identfy genes differentially expressed in choroid plexus tumor cells.
2009-02-01 | E-GEOD-14098 | biostudies-arrayexpress
Project description:Gene expression data from normal mouse choroid plexus, choroid plexus papilloma and choroid plexus carcinoma
| PRJNA521552 | ENA
Project description:A subset of infants and adults with hemorrhagic stroke and intraventricular hemorrhage (IVH) ultimately develop a life-threatening accumulation of cerebrospinal fluid (CSF), termed post-hemorrhagic hydrocephalus (PHH). An incomplete understanding of this variably progressive condition has hampered the development of new therapies beyond serial neurosurgical interventions. We describe an adeno-associated viral (AAV) gene augmentation approach leveraging the Na-K-Cl cotransporter, NKCC1, to enhance a choroid plexus (ChP) mechanism of CSF surveillance, potassium homeostasis, and water movement to drive decreases in ventricle size in embryonic, neonatal, and adult mouse models of IVH. Intraventricular blood led to increased CSF [K+], triggered cytosolic calcium in ChP epithelial cells, and was followed by NKCC1 activation. ChP-targeted AAV-NKCC1 rapidly reversed blood-induced ventriculomegaly and led to persistently increased CSF clearance capacity, validating the model and treating the most salient clinical features of PHH. NKCC1 is a bi-directional cotransporter, and these data demonstrate that NKCC1 activation triggered a trans-choroidal, NKCC1-dependent CSF ion/water clearance out of the ventricle. Inactive, phosphodeficient AAV-NKCC1-NT51 failed to mitigate ventriculomegaly, indicating that the beneficial effects of NKCC1 augmentation required both elevated CSF [K+] and upstream activation via phosphorylation. Excessive CSF [K+] fluctuations correlated with permanent shunting outcome in humans following hemorrhagic stroke, suggesting potential therapeutic benefits. Collectively, these data highlight a novel role for the ChP in rapid compensation for alterations in CSF homeostasis following IVH and demonstrate the utility of targeted gene therapy to mitigate intracranial fluid accumulation following hemorrhage.
2024-05-24 | PXD039738 | Pride
Project description:Choroid plexus secretes cerebrospinal fluid important for brain development and homeostasis. The OTX2 homeoprotein is critical for choroid plexus development and remains highly expressed in adult choroid plexus. Through RNA sequencing analyses of constitutive and conditional knockdown adult mouse models, we reveal putative roles for OTX2 in choroid plexus function, including cell signaling and adhesion, and show that it regulates the expression of factors secreted into cerebrospinal fluid, notably transthyretin. We also show that Otx2 expression impacts choroid plexus immune and stress responses, and also affects splicing which leads to changes in mRNA isoforms of proteins implicated in oxidative stress response and DNA repair. Through mass spectrometry analysis of OTX2 protein partners in the choroid plexus, and in known non-cell autonomous target regions such as visual cortex and subventricular zone, we identified putative targets involved in cell adhesion, chromatin structure and RNA processing. Thus, OTX2 retains important roles in choroid plexus function and brain homeostasis throughout life.
2021-08-31 | GSE157386 | GEO