title: Spatially heterogeneous choroid plexus transcriptomes encode positional identity and contribute to regional CSF production.
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.
authors: Department of Pathology, and Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts 02118.
authors: Melody P
authors: MP
authors: Lun
authors: Division of Genetics, Boston Children's Hospital, Boston, Massachusetts 02115.
authors: Matthew B
authors: http://orcid.org/0000-0001-6909-5712
authors: MB
authors: Johnson
authors: Department of Pathology, and.
authors: Kevin G
authors: KG
authors: Broadbelt
authors: Department of Pathology and Laboratory Medicine, University of California Irvine School of Medicine, Irvine, California 92697.
authors: Momoko
authors: M
authors: Watanabe
authors: Department of Pathology and Laboratory Medicine, University of California Irvine School of Medicine, Irvine, California 92697.
authors: Young-Jin
authors: YJ
authors: Kang
authors: Department of Pathology, and.
authors: Kevin F
authors: KF
authors: Chau
authors: Department of Pathology, and.
authors: Mark W
authors: MW
authors: Springel
authors: Department of Pathology, and.
authors: Alexandra
authors: A
authors: Malesz
authors: Department of Neurobiology and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut 06510.
authors: André M M
authors: AM
authors: Sousa
authors: Department of Neurobiology and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut 06510.
authors: Mihovil
authors: http://orcid.org/0000-0002-6056-9579
authors: M
authors: Pletikos
authors: Department of Pathology, and Department of Biochemistry, Federal University of São Paulo, São Paulo 04039, Brazil, and.
authors: Tais
authors: T
authors: Adelita
authors: Tai
authors: http://orcid.org/0000-0003-3871-3172
authors: T
authors: Adelita
authors: Department of Pathology, and.
authors: Monica L
authors: ML
authors: Calicchio
authors: Pulmonary and Critical Care Medicine, Department of Medicine, Washington University, St Louis, Missouri 63110.
authors: Yong
authors: Y
authors: Zhang
authors: Pulmonary and Critical Care Medicine, Department of Medicine, Washington University, St Louis, Missouri 63110.
authors: Michael J
authors: MJ
authors: Holtzman
authors: Department of Pathology, and.
authors: Hart G W
authors: HG
authors: Lidov
authors: Department of Neurobiology and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut 06510.
authors: Nenad
authors: http://orcid.org/0000-0003-0966-9619
authors: N
authors: Sestan
authors: Department of Pathology, and.
authors: Hanno
authors: H
authors: Steen
authors: Department of Pathology and Laboratory Medicine, University of California Irvine School of Medicine, Irvine, California 92697.
authors: Edwin S
authors: http://orcid.org/0000-0001-5130-781X
authors: ES
authors: Monuki
authors: Department of Pathology, and maria.lehtinen@childrens.harvard.edu.
authors: Maria K
authors: MK
authors: Lehtinen
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D002831:Choroid Plexus / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D020546:Fourth Ventricle / Q000378:metabolism*; D006801:Humans; D020547:Lateral Ventricles / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D059467:Transcriptome
keywords: cerebrospinal fluid; choroid plexus; next-generation sequencing