Single-cell transcriptomic profling of the aging mouse choroid plexus
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE232782 | GEO | 2025/01/13
REPOSITORIES: GEO
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Project description:The choroid plexus (CP) constitutes one of the blood–brain barriers – the blood cerebrospinal fluid barrier. It is formed by a monolayer of epithelial cells located within the brain ventricles and in addition to be responsible for the formation of the cerebrospinal fluid (CSF) is ideally positioned to transmit signals into and out of the brain. Specifically, here, we evaluated the overall kinetic response of the mouse CP to peripheral administration of lipopolysaccharide (LPS) that is the Gram-negative bacteria cell wall. This study shows that as soon as 1h after the injection, the CP responds by altering the expression of several genes. This response reaches a maximum at 3h and returns to the basal profile for most of the transcripts at 72h. To do this analysis we compared the CP transcriptome of LPS injected animals with the CP transcriptome of saline injected animals and using this we also dissect the CP basal transcriptome. From this analysis we confirm that the genes most highly expressed were those implicated in energy metabolism (oxidative phosphorylation, glycolysis/gluconeogenesis) and in ribosomal function, which is in agreement with the secretory nature of the CP. Finally, we also describe genes not previously identified as being expressed in the basal CP. Gene expression study in choroid plexus. Time series after acute LPS treatment
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Project description:The choroid plexus produces cerebrospinal fluid (CSF) by transport of electrolytes and water from the vasculature to the brain ventricles. The choroid plexus plays additional roles in brain development and homeostasis by secreting neurotrophic molecules, and by serving as a CSF-blood barrier and immune interface. Prior studies have identified transporters on the epithelial cells that transport water and ions into the ventricles and tight junctions involved in the CSF-blood barrier. Yet, how the choroid plexus epithelial cells maintain the brain ventricle system and control brain physiology remain unresolved. To provide novel insights into the physiological roles of the choroid plexus, we use juvenile and adult zebrafish as model systems. Upon histological and transcriptomic analyses, we first identified that the zebrafish choroid plexus is highly conserved with the mammalian choroid plexus and that it expresses all transporters necessary for CSF secretion. Using novel genetic lines, we also identified that the choroid plexus secretes proteins into the CSF. Next, we generated a transgenic line allowing us to ablate specifically the epithelial cells in the choroid plexus. Using the ablation system, we identified a reduction of the ventricular sizes, but no alterations of the CSF-blood barrier. Altogether, our findings identified that the zebrafish choroid plexus is evolutionarily conserved and critical for maintaining the size and homeostasis of the brain ventricles.
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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.
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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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Project description:The choroid plexus (CP) constitutes one of the blood–brain barriers – the blood cerebrospinal fluid barrier. It is formed by a monolayer of epithelial cells located within the brain ventricles and in addition to be responsible for the formation of the cerebrospinal fluid (CSF) is ideally positioned to transmit signals into and out of the brain. Specifically, here, we evaluated the overall kinetic response of the mouse CP to peripheral administration of lipopolysaccharide (LPS) that is the Gram-negative bacteria cell wall. This study shows that as soon as 1h after the injection, the CP responds by altering the expression of several genes. This response reaches a maximum at 3h and returns to the basal profile for most of the transcripts at 72h. To do this analysis we compared the CP transcriptome of LPS injected animals with the CP transcriptome of saline injected animals and using this we also dissect the CP basal transcriptome. From this analysis we confirm that the genes most highly expressed were those implicated in energy metabolism (oxidative phosphorylation, glycolysis/gluconeogenesis) and in ribosomal function, which is in agreement with the secretory nature of the CP. Finally, we also describe genes not previously identified as being expressed in the basal CP.
2010-08-20 | GSE23714 | GEO
Project description:A sheet of choroid plexus epithelial cells extends into each cerebral ventricle and secretes signaling factors into the cerebrospinal fluid (CSF). To evaluate whether differences in the CSF proteome across ventricles arise, in part, from regional differences in choroid plexus gene expression, we defined the transcriptome of lateral ventricle (telencephalic) vs. fourth ventricle (hindbrain) choroid plexus. We find that positional identities of mouse, macaque, and human choroid plexi derive from gene expression domains that parallel their axial tissues of origin. We then show that molecular heterogeneity between telencephalic and hindbrain choroid plexi contributes to region-specific, age-dependent protein secretion in vitro. Transcriptome analysis of FACS-purified choroid plexus epithelial cells also predicts their cell type-specific secretome. Spatial domains with distinct protein expression profiles were observed within each choroid plexus. We propose that regional differences between choroid plexi contribute to dynamic signaling gradients across the mammalian cerebroventricular system.
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Project description:The choroid plexus (ChP) in each brain ventricle produces cerebrospinal fluid (CSF) and forms the blood-CSF barrier. We apply single cell and single nuclei sequencing to identify region and age specific shifts in gene expression of the constituent cell types of the choroid plexus. First, we sequenced whole cells (15,620) from each ventricle (lateral, third and fourth) of the embryonic mouse brain (Embryonic day (E) 16.5). Our analyses and validation of gene (smFISH) and protein (immunohistochemistry) expression combined with spatial mapping (confocal imaging) revealed the identity and location of major cell types, subtypes, proliferating cells, progenitor populations and regionalized gene expression, across each ventricle in the developing brain. Next, to track age-dependent shifts in the choroid plexus properties, we performed single nuclei sequencing (83,040) across each ventricle of the embryonic (E16.5), adult (4 months) and aging (20 months) mouse brain. Epithelial and mesenchymal cells showed regionalized gene expression patterns by ventricle, starting at embryonic stages and persisting with age. Dramatic transcriptional shifts were found with maturation (embryonic to adult) and a smaller shift within each aged cell type. With aging, epithelial cells upregulated host defense programs and resident macrophages enhanced expression of IL-1b signaling genes. Our atlas revealed ChP brain barrier cellular diversity, architecture and signaling across ventricles during development, maturation and aging.
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Project description:3 mice per timepoint (9am and 9pm) with FoxJ1-Cre x TRAP-BAC-EGFP:L10a dissected choroid plexus. Transmission and secretion of signals via the choroid plexus (ChP) brain barrier can modulate brain states via regulation of cerebrospinal fluid (CSF) composition. Here, we developed a platform to analyze diurnal variations in male mouse ChP and CSF. Ribosome profiling of ChP epithelial cells revealed diurnal translatome differences in metabolic machinery, secreted proteins, and barrier components. Using ChP and CSF metabolomics and blood-CSF barrier analyses, we observed diurnal changes in metabolites and cellular junctions. We then focused on transthyretin (TTR), a diurnally regulated thyroid hormone chaperone secreted by the ChP. Diurnal variation in ChP TTR depended on Bmal1 clock gene expression. We achieved real-time tracking of CSF-TTR in awake TtrmNeonGreen mice via multi-day intracerebroventricular fiber photometry. Diurnal changes in ChP and CSF TTR levels correlated with CSF thyroid hormone levels. These datasets highlight an integrated platform for investigating diurnal control of brain states by the ChP and CSF.
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Project description:Laser capture microdissected choroid plexuses were obtained and expression arrays were generated to investigate gene expression in ApoE-Knockin choroid plexuses; the choroid plexus forms the cerebrospinal fluid, the cerebrospinal fliod barrier, functions as the major gateway for blood-born leukocytes to enter the brain in degenerative and inflammatory brain diseases, and the principal neuroimmune interface in the brain. We found lipid deposits in the aged choroid plexus of hyperlipidemic ApoE4-Knockin mice but none in normolipidemic ApoE4-Knockin or normolipidemic or hyperlipidemic ApoE3-Knockin control choroid plexuses. Here, we studied the functional impact and gene epressions these choroid plexuses.
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