Spatially heterogeneous choroid plexus transcriptomes encode positional identity and contribute to regional cerebrospinal fluid production

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. Overall design: Two-factor design with two levels per factor and n=2 biological replicates. Lateral (telencephalic) and fourth (hindbrain) choroid plexus samples are paired in that they are isolated from the same brains.

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Lun MP, Johnson MB, Broadbelt KG, Watanabe M, Kang YJ, Chau KF, Springel MW, Malesz A, Sousa AM, Pletikos M, Adelita T, Calicchio ML, Zhang Y, Holtzman MJ, Lidov HG, Sestan N, Steen H, Monuki ES, Lehtinen MK