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

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, Tai Adelita, Monica L. Calicchio, Yong Zhang, Michael J. Holtzman, Hart G.W. Lidov, Nenad Sestan, Hanno Steen, Edwin S. Monuki, Maria K. Lehtinen

Research output: Contribution to journalArticle

45 Scopus citations

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.

Original languageEnglish
Pages (from-to)4903-4916
Number of pages14
JournalJournal of Neuroscience
Volume35
Issue number12
DOIs
StatePublished - Jan 1 2015

Keywords

  • Cerebrospinal fluid
  • Choroid plexus
  • Next-generation sequencing

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    Lun, M. P., Johnson, M. B., Broadbelt, K. G., Watanabe, M., Kang, Y. J., Chau, K. F., Springel, M. W., Malesz, A., Sousa, A. M. M., Pletikos, M., Adelita, T., Calicchio, M. L., Zhang, Y., Holtzman, M. J., Lidov, H. G. W., Sestan, N., Steen, H., Monuki, E. S., & Lehtinen, M. K. (2015). Spatially heterogeneous choroid plexus transcriptomes encode positional identity and contribute to regional CSF production. Journal of Neuroscience, 35(12), 4903-4916. https://doi.org/10.1523/JNEUROSCI.3081-14.2015