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Choroid plexus organoids predict CNS drug permeability and reveal human CSF proteins produced by specialized cell types

ABSTRACT: Choroid plexus organoids predict CNS drug permeability and reveal human CSF proteins produced by specialized cell types

PROVIDER: PRJNA634025 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11816759_1.fastq.gz	Fastqsanger.gz
	SRR11816759_2.fastq.gz	Fastqsanger.gz
	SRR11816760_1.fastq.gz	Fastqsanger.gz
	SRR11816760_2.fastq.gz	Fastqsanger.gz
	SRR11816761_1.fastq.gz	Fastqsanger.gz

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Choroid plexus organoids predict CNS drug permeability and reveal human CSF proteins produced by specialized cell types

Project description:The choroid plexus (ChP) is a protective epithelial barrier that filters blood and secretes cerebrospinal fluid (CSF), an important fluid for nutrient maintenance in the brain and transport of signalling molecules. Here, we establish human ChP organoids with a selective epithelial barrier that secrete CSF-like fluid in self-contained compartments. We show that this in vitro barrier exhibits the same selectivity to small molecules as the in vivo counterpart, and that ChP-CSF organoids can predict CNS permeability of novel compounds. Characterization of the transcriptomic signature of ChP organoids and the proteomic make-up of the CSF-like fluid demonstrate a high degree of similarity to the in vivo counterpart. We leverage the fact that these organoids represent the tissue in isolation to examine their cellular make-up, and explore the specialized epithelial subtypes involved in de novo production of key CSF components. This reveals the presence of heterogeneous epithelial ChP populations, including a newly identified myoepithelial cell type, and uncovers human-specific factors secreted by these specialized cell types.

2020-06-11 | GSE150903 | GEO

Gene expression data from normal mouse choroid plexus, choroid plexus papilloma and choroid plexus carcinoma

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

Gene expression profiles obtained from laser-microdissected human choroid plexus papilloma cells

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

Gene expression data from normal mouse choroid plexus, choroid plexus papilloma and choroid plexus carcinoma

Project description:Gene expression data from normal mouse choroid plexus, choroid plexus papilloma and choroid plexus carcinoma

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Effects of gut microbiota on gene expression in the choroid plexus

Project description:Accumulating evidence indicates that gut microbiota dysbiosis is associated with increased blood-brain barrier (BBB) permeability and contributes to Alzheimer’s disease (AD) pathogenesis. In contrast, the influence of gut microbiota on the blood-cerebrospinal fluid (CSF) barrier has not yet been studied. Here, RNA-seq analysis of choroid plexus tissues of normal colonized specific pathogen-free (SPF) versus decolonized antibiotics-treated mice revealed that the barrier function of choroid plexus is affected by the absence of gut microbiota in the AB mice.

2023-06-05 | GSE228655 | GEO

OTX2 homeoprotein regulates adult choroid plexus activity

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

Transcriptome profiling of developing choroid plexus and FoxJ1-/- choroid plexus

Project description:Transcriptome profiling of developing choroid plexus and FoxJ1-/- choroid plexus

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Proteomics profiling of pediatric choroid plexus tumors

Project description:Aggresome is a para nuclear inclusion body that functions as a storage compartment for misfolded proteins. Our previous work revealed the presence of aggresomes in pediatric choroid plexus tumors (CPT). CPTs are rare neoplasms comprised of three pathological subgroups; choroid plexus carcinoma (CPC), a grade III tumor, atypical choroid plexus papilloma (ACPP), a grade II tumor, and choroid plexus papilloma (CPP), a grade I tumor. In the current study, we aimed to investigate the prognostic value of aggresomes-positivity and its correlation to the pathological and molecular subtypes. The proteomics profiling of 21 CPT pediatric samples was investigated using ABSciex Triple TOF 5600+ mass spectrometer.

2021-02-11 | PXD021076 | Pride

Day-night fluctuations in choroid plexus transcriptomics and CSF metabolomics

Project description:Male Sprague-Dawley rats, kept in light-controlled 12:12 conditions, presented with diurnally modulated CSF metabolite composition. This change was accompanied with differential expression of 2778 genes within the choroid plexus, with several plasma membrane transporters and CLOCK-associated genes diurnally modulated.

2023-07-31 | GSE228866 | GEO

Methylation profiling of pediatric choroid plexus tumors

Project description:Aggresome is a para nuclear inclusion body that functions as a storage compartment for misfolded proteins. Our previous work revealed the presence of aggresomes in pediatric choroid plexus tumors (CPT). CPTs are rare neoplasms comprised of three pathological subgroups; choroid plexus carcinoma (CPC), a grade III tumor, atypical choroid plexus papilloma (ACPP), a grade II tumor, and choroid plexus papilloma (CPP), a grade I tumor. In the current study, we aimed to investigate the prognostic value of aggresomes-positivity and its correlation to the pathological and molecular subtypes. The genome-wide methylation profile of 42 CPT pediatric samples was investigated using Illumina Infinium Methylation EPIC BeadChip array.

2021-01-21 | GSE156090 | GEO

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