Human CNS barrier-forming organoids with cerebrospinal fluid production

被引:277
作者
Pellegrini, Laura [1 ]
Bonfio, Claudia [1 ]
Chadwick, Jessica [1 ]
Begum, Farida [1 ]
Skehel, Mark [1 ]
Lancaster, Madeline A. [1 ]
机构
[1] MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England
基金
英国医学研究理事会; 欧洲研究理事会;
关键词
CENTRAL-NERVOUS-SYSTEM; CHOROID-PLEXUS; ALZHEIMERS-DISEASE; PROTEOMIC ANALYSIS; MATRIX METALLOPROTEINASES; CEREBRAL ORGANOIDS; APOLIPOPROTEIN-E; CSF BIOMARKER; TUMOR-MARKERS; SPINAL-FLUID;
D O I
10.1126/science.aaz5626
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:159 / +
页数:58
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