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

Area of Science:

• Neuroscience
• Molecular Biology
• Genomics

Background:

• The choroid plexus, located in cerebral ventricles, secretes signaling factors into the cerebrospinal fluid (CSF).
• Potential regional variations in choroid plexus gene expression and their impact on CSF proteome are not fully understood.

Purpose of the Study:

• To investigate whether regional differences in choroid plexus gene expression contribute to variations in the CSF proteome across different brain ventricles.
• To define the transcriptomes of lateral and fourth ventricle choroid plexi and assess their molecular heterogeneity.

Main Methods:

• Comparative transcriptome analysis of choroid plexus from lateral (telencephalic) and fourth (hindbrain) ventricles in mouse, macaque, and human.
• In vitro studies to assess region-specific protein secretion from choroid plexus epithelial cells.
• Transcriptome analysis of Fluorescence-Activated Cell Sorting (FACS)-purified choroid plexus epithelial cells.

Main Results:

• Positional identities of choroid plexi are linked to gene expression domains reflecting their axial tissue origins.
• Molecular differences between telencephalic and hindbrain choroid plexi drive region-specific, age-dependent protein secretion.
• Distinct spatial domains with unique protein expression profiles exist within individual choroid plexi.
• Cell-type-specific secretomes can be predicted from choroid plexus epithelial cell transcriptomes.

Conclusions:

• Regional heterogeneity in choroid plexi contributes to region-specific protein secretion into the CSF.
• These molecular differences establish dynamic signaling gradients across the mammalian cerebroventricular system.
• Understanding choroid plexus heterogeneity is crucial for deciphering CSF signaling and brain function.