An integrated multi-omic atlas of the choroid plexus highlights conserved molecular programs of epithelial function

The choroid plexus (ChP) plays a vital role in maintaining cerebrospinal fluid (CSF) homeostasis by producing the fluid, preserving the blood-CSF barrier, and regulating signaling factors. Despite its significance, the conserved molecular programs of ChP epithelial function across species and conditions remain largely unexplored. This study aimed to address this knowledge gap by integrating eight single-cell/nucleus RNA-seq datasets from both mouse and human ChP tissues.

The integration of these datasets led to the creation of a comprehensive multi-species ChP atlas, encompassing major epithelial, stromal, vascular, and immune cell populations. By comparing datasets across experiments, researchers identified a set of conserved epithelial gene programs that encompass ion transport, barrier function, ciliogenesis, and secretory signaling. This conserved epithelial gene program was further enriched by highlighting understudied genes like CLIC6 and VAT1L.

Further analysis using co-expression network analysis revealed conserved epithelial meta-programs. Additionally, transcription factor regulatory inference identified OTX2, MSX1, and GLIS3 as key regulators of epithelial gene expression across the ChP tissues. To gain spatial context, the researchers generated a novel Visium HD spatial transcriptomic atlas of the mouse fourth-ventricle ChP, allowing for orthogonal validation of the previously identified epithelial modules.

Lastly, a cross-tissue analysis revealed substantial transcriptional overlap between ChP and retinal pigment epithelium. This overlap included shared epithelial genes and regulatory relationships mediated by OTX2. The researchers conclude that these findings define conserved molecular programs of ChP epithelial specialization, provide candidate regulators for functional investigation, and offer an integrated cross-species and spatial resource for further study of ChP physiology.