Human CNS barrier-forming organoids with cerebrospinal fluid production
Human CNS barrier-forming organoids with cerebrospinal fluid production
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DOI：
10.1126/science.aaz5626
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发表时间：
2020-07-10
期刊：
影响因子：
56.9
通讯作者：
Lancaster, Madeline A.
中科院分区：
文献类型：
--
作者：
Pellegrini, Laura;Bonfio, Claudia;Lancaster, Madeline A.
脑脊液(CSF)是一种重要的液体，提供营养和信号分子，并清除大脑中的有毒副产物。脑脊液是由脉络丛(CHP)产生的，脉络丛是一种保护性的上皮屏障，也可以阻止有毒分子或药物从血液中自由进入。在这里，我们建立了具有选择性屏障的人CHP类有机化合物，并在独立的隔室中进行脑脊液样液体分泌。我们发现，这种体外屏障对小分子的选择性与体内CHP相同，CHP-CSF类有机物可以预测新化合物的中枢神经系统(CNS)通透性。CHP-CSF类有机物的转录和蛋白质组特征表明与体内的CHP具有高度的相似性。最后，单细胞转录组和蛋白质组分析的交集揭示了由以前未确定的特化上皮亚型产生的关键人类脑脊液成分。
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.