Spatially Heterogeneous Choroid Plexus Transcriptomes Encode Positional Identity and Contribute to Regional CSF Production
Lun, Melody P.
Johnson, Matthew B.
Broadbelt, Kevin G.
Chau, Kevin F.
Springel, Mark W.
Sousa, Andre M. M.
Adelita, Tai [UNIFESP]
Calicchio, Monica L.
Holtzman, Michael J.
Lidov, Hart G. W.
Monuki, Edwin S.
Lehtinen, Maria K.
Is part ofJournal of Neuroscience
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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.
CitationJournal of Neuroscience. Washington: Soc Neuroscience, v. 35, n. 12, p. 4903-4916, 2015.
SponsorshipABTA Medical Student Summer Fellowship
Glenn/AFAR Scholarship for Research in the Biology of Aging
Nancy Lurie Marks Family Foundation Postdoctoral Fellowship
California Institute for Regenerative Medicine (CIRM) Training Grant
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
UCI Institute for Clinical and Translational Science Pilot Project Award
Pediatric Hydrocephalus Foundation
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