Journal
SCIENCE
Volume 369, Issue 6500, Pages 159-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaz5626
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Funding
- Medical Research Council [MC_UP_1201/9]
- European Research Council [ERC STG 757710]
- MRC [MC_UP_1201/9] Funding Source: UKRI
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Cerebrospinal fluid (CSF) is a vital liquid, providing nutrients and signaling molecules and clearing out toxic by-products from the brain. The CSF is produced by the choroid plexus (ChP), a protective epithelial barrier that also prevents free entry of toxic molecules or drugs from the blood. Here, we establish human ChP organoids with a selective barrier and CSF-like fluid secretion in self-contained compartments. We show that this in vitro barrier exhibits the same selectivity to small molecules as the ChP in vivo and that ChP-CSF organoids can predict central nervous system (CNS) permeability of new compounds. The transcriptomic and proteomic signatures of ChP-CSF organoids reveal a high degree of similarity to the ChP in vivo. Finally, the intersection of single-cell transcriptomics and proteomic analysis uncovers key human CSF components produced by previously unidentified specialized epithelial subtypes.
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