The choroid plexus (ChP) in each brain ventricle produces cerebrospinal fluid (CSF) and forms the blood-CSF barrier. Here, we construct a single-cell and spatial atlas of each ChP in the developing, adult, and aged mouse brain. We delineate diverse cell types, subtypes, cell states, and expression programs in epithelial and mesenchymal cells across ages and ventricles. In the developing ChP, we predict a common progenitor pool for epithelial and neuronal cells, validated by lineage tracing. Epithelial and fibroblast cells show regionalized expression by ventricle, starting at embryonic stages and persisting with age, with a dramatic transcriptional shift with maturation, and a smaller shift in each aged cell type. With aging, epithelial cells upregulate host-defense programs, and resident macrophages upregulate interleukin-1β (IL-1β) signaling genes. Our atlas reveals cellular diversity, architecture and signaling across ventricles during development, maturation, and aging of the ChP-brain barrier.

Broad Institute of MIT and Harvard Cambridge MA 02142 USA; Edmond and Lily Safra Center for Brain Sciences Hebrew University of Jerusalem Jerusalem 9190401 Israel

Broad Institute of MIT and Harvard Cambridge MA 02142 USA; Howard Hughes Medical Institute Chevy Chase MD 20815 USA; McGovern Institute for Brain Research Massachusetts Institute of Technology Cambridge MA 02139 USA; Department of Brain and Cognitive Sciences and Department of Biological Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA

Czech Centre for Phenogenomics and Laboratory of Transgenic Models of Diseases Institute of Molecular Genetics of the CAS Prague 142 20 Czech Republic

Department of Experimental Biology Faculty of Science Masaryk University Brno 611 37 Czech Republic

Department of Pathology Boston Children's Hospital Boston MA 02115 USA

Department of Pathology Boston Children's Hospital Boston MA 02115 USA; Graduate Program in Biophysics Harvard University Cambridge MA 02115 USA

Edmond and Lily Safra Center for Brain Sciences Hebrew University of Jerusalem Jerusalem 9190401 Israel

Klarman Cell Observatory Broad Institute of MIT and Harvard Cambridge MA 02142 USA

Klarman Cell Observatory Broad Institute of MIT and Harvard Cambridge MA 02142 USA; Broad Institute of MIT and Harvard Cambridge MA 02142 USA; Howard Hughes Medical Institute Chevy Chase MD 20815 USA; Koch Institute of Integrative Cancer Research Department of Biology Massachusetts Institute of Technology Cambridge MA 02142 USA

Klarman Cell Observatory Broad Institute of MIT and Harvard Cambridge MA 02142 USA; Department of Systems Biology Harvard Medical School Boston MA 02115 USA

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Regulation of choroid plexus development and its functions

MEIS-WNT5A axis regulates development of fourth ventricle choroid plexus

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