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

空间异质性脉络丛转录组编码位置身份并促进区域脑脊液的产生

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作者:Melody P Lun, Matthew B Johnson, Kevin G Broadbelt, Momoko Watanabe, Young-Jin Kang, Kevin F Chau, Mark W Springel, Alexandra Malesz, André M M Sousa, Mihovil Pletikos, Tais Adelita, Monica L Calicchio, Yong Zhang, Michael J Holtzman, Hart G W Lidov, Nenad Sestan, Hanno Steen, Edwin S Monuki, Maria

Abstract

A sheet of choroid plexus epithelial cells extends into each cerebral ventricle and secretes signaling factors into the 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) versus 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.

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