GSE168704
A cellular and spatial map of the choroid plexus across brain ventricles and ages
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. Overall design: We sequenced whole cells isolated from lateral, third and fourth ventricle of embryonic brains (E16.5, CD-1) in triplicate. We sequenced whole nuclei isolated from each ventricle of embryonic (E16.5), adult (4 months post natal) and aging (20 months post natal) mouse (C57BL/6J) brains.