Project description:We used microarrays to reveal the global expression profiles of young and old whole lateral ventricle choroid plexus tissue. RNA was isolated from whole lateral ventricle choroid plexus tissue followed by RNA amplification and hybridization on Affymetrix microarrays. Each sample contains both lateral ventricle choroid plexi from one male CD1 mouse. A total of six samples (three biological replicates from 2 different ages) were analyzed.
Project description:We investigated gene expression profile of the Brain's choroid plexus and other organs of young and aged mice. Additionally, we analysed gene expression profile of the choroid plexus in iso- and heterochronic- parabiosis settings of young and aged mice. 75 samples
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.
Project description:We investigated gene expression profile of the Brain's choroid plexus and other organs of young and aged mice. Additionally, we analysed gene expression profile of the choroid plexus in iso- and heterochronic- parabiosis settings of young and aged mice.
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.
Project description:Healthy brain development and function highly depend on the choroid plexus. Temporal alterations in the cellular landscape and gene expression of choroid plexus cells, whether in health or disease, can alter immune cell trafficking in the brain and cerebrospinal fluid composition, ultimately impacting brain dynamics. Here, we performed a comprehensive multi-omics analysis—including bulk and single-cell transcriptomics and epigenomics—of the lateral ventricle choroid plexus across early postnatal and adult stages in mice and rats. We uncovered striking fluctuations in the choroid plexus cellular composition from neonatal to adult stages, accompanied by transcriptional remodeling of all main cell types. Immune profiling revealed a marked increase in immune cells in adulthood and an altered cell-type diversity through time. Surprisingly, we observed an early activation of host-defense genes in choroid plexus cell, beginning in the neonatal period and progressively increasing into young adulthood. Epithelial cells exhibited subtype diversity and plasticity, with distinct gene expression programs and chromatin accessibility profiles emerging over time. Notably, we identified a previously unrecognized epithelial cell subtype with unique gene markers suggesting a specialized function. Ligand-receptor interaction analysis revealed a progressive remodeling of cellular crosstalk networks during CP maturation, suggesting dynamic intercellular signaling as the tissue develops. Our study offers a comprehensive atlas of gene activity and chromatin accessibility in the lateral ventricle CP cells, providing a valuable resource to guide future efforts in targeting gene expression at the CP for therapeutical purposes.
Project description:Healthy brain development and function highly depend on the choroid plexus. Temporal alterations in the cellular landscape and gene expression of choroid plexus cells, whether in health or disease, can alter immune cell trafficking in the brain and cerebrospinal fluid composition, ultimately impacting brain dynamics. Here, we performed a comprehensive multi-omics analysis—including bulk and single-cell transcriptomics and epigenomics—of the lateral ventricle choroid plexus across early postnatal and adult stages in mice and rats. We uncovered striking fluctuations in the choroid plexus cellular composition from neonatal to adult stages, accompanied by transcriptional remodeling of all main cell types. Immune profiling revealed a marked increase in immune cells in adulthood and an altered cell-type diversity through time. Surprisingly, we observed an early activation of host-defense genes in choroid plexus cell, beginning in the neonatal period and progressively increasing into young adulthood. Epithelial cells exhibited subtype diversity and plasticity, with distinct gene expression programs and chromatin accessibility profiles emerging over time. Notably, we identified a previously unrecognized epithelial cell subtype with unique gene markers suggesting a specialized function. Ligand-receptor interaction analysis revealed a progressive remodeling of cellular crosstalk networks during CP maturation, suggesting dynamic intercellular signaling as the tissue develops. Our study offers a comprehensive atlas of gene activity and chromatin accessibility in the lateral ventricle CP cells, providing a valuable resource to guide future efforts in targeting gene expression at the CP for therapeutical purposes.
Project description:Healthy brain development and function highly depend on the choroid plexus. Temporal alterations in the cellular landscape and gene expression of choroid plexus cells, whether in health or disease, can alter immune cell trafficking in the brain and cerebrospinal fluid composition, ultimately impacting brain dynamics. Here, we performed a comprehensive multi-omics analysis—including bulk and single-cell transcriptomics and epigenomics—of the lateral ventricle choroid plexus across early postnatal and adult stages in mice and rats. We uncovered striking fluctuations in the choroid plexus cellular composition from neonatal to adult stages, accompanied by transcriptional remodeling of all main cell types. Immune profiling revealed a marked increase in immune cells in adulthood and an altered cell-type diversity through time. Surprisingly, we observed an early activation of host-defense genes in choroid plexus cell, beginning in the neonatal period and progressively increasing into young adulthood. Epithelial cells exhibited subtype diversity and plasticity, with distinct gene expression programs and chromatin accessibility profiles emerging over time. Notably, we identified a previously unrecognized epithelial cell subtype with unique gene markers suggesting a specialized function. Ligand-receptor interaction analysis revealed a progressive remodeling of cellular crosstalk networks during CP maturation, suggesting dynamic intercellular signaling as the tissue develops. Our study offers a comprehensive atlas of gene activity and chromatin accessibility in the lateral ventricle CP cells, providing a valuable resource to guide future efforts in targeting gene expression at the CP for therapeutical purposes.
Project description:To characterize underlying changes in the retinal pigment epithelium (RPE)/choroid with age, we produced gene expression profiles for the RPE/choroid and compared the transcriptional profiles of the RPE/choroid from young and old mice. The changes in the aged RPE/choroid suggest that the tissue has become immunologically active. Such phenotypic changes in the normal aged RPE/choroid may provide a background for the development of age-related macular degeneration. Experiment Overall Design: We compared the gene expression of retinal pigmental epithelium/choroid from young and old animals. There were 4 samples from young mice and 4 samples from old mice. Each sample contained 4 retinal pigmental epithelium/choroid from 2 animals