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Canonical Wnt signaling exerts bidirectional control on choroid plexus epithelial development

ABSTRACT: Canonical Wnt signaling exerts bidirectional control on choroid plexus epithelial development

PROVIDER: PRJNA683014 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13208268_1.fastq.gz	Fastqsanger.gz
	SRR13208268_2.fastq.gz	Fastqsanger.gz
	SRR13208269_1.fastq.gz	Fastqsanger.gz
	SRR13208269_2.fastq.gz	Fastqsanger.gz
	SRR13208270_1.fastq.gz	Fastqsanger.gz

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Canonical Wnt signaling exerts bidirectional control on choroid plexus epithelial development

Project description:The choroid plexus (CP) secretes cerebrospinal fluid and is critical for the development and function of the brain. In the telencephalon, the CP epithelium (CPe) arises from the Wnt- and Bmp- expressing cortical hem. We examined the role of canonical Wnt signaling in CPe development and report that the mouse and human embryonic CPe expresses molecules in this pathway. Either loss of function or constitutive activation of β-catenin, a key mediator of canonical Wnt signaling, causes a profound disruption of mouse CPe development. Loss of β-catenin results in a dysmorphic CPe, while constitutive activation of β-catenin causes a loss of CPe identity and a transformation of this tissue to a hippocampal-like identity. Aspects of this phenomenon are recapitulated in human embryonic stem cell (hESC)-derived organoids. Our results indicate that canonical Wnt signaling is required in a precisely regulated manner for normal CP development in the mammalian brain.

2021-11-01 | GSE162784 | GEO

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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

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

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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.

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

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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.

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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.

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Methylation profiling of pediatric choroid plexus tumors

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Single Nucleus RNAseq dissection of choroid plexus tumor cell heterogeneity

Project description:To examine the cellular and transcriptional heterogeneity of choroid plexus tumors we determined the single nucleus transcriptomes of 23,906 nuclei from normal choroid plexus and choroid plexus tumors. The resulting cellular atlas profiles cellular and transcriptional heterogeneity, copy number alterations, and cell-cell interaction networks in normal and cancerous choroid plexus. We observe changes in choroid plexus tumor epithelial cell gene transcription that correlate with genome wide methylation profiles. In addition, we characterize tumor-grade-specific tumor microenvironments that include altered macrophage and mesenchymal cell states, as well as changes in extracellular matrix components.

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