Multi-omics Profiling of the Lateral Ventricle Choroid Plexus Reveals Temporal Cellular Remodeling, Early Immune Gene Activation, and a Novel Epithelial Subtype [snMultiome]

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.