Fused cerebral organoids model interactions between brain regions

被引:536
作者
Bagley, Joshua A. [1 ]
Reumann, Daniel [1 ]
Bian, Shan [1 ]
Levi-Strauss, Julie [1 ]
Knoblich, Juergen A. [1 ]
机构
[1] Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna, Austria
基金
奥地利科学基金会; 欧洲研究理事会;
关键词
PLURIPOTENT STEM-CELLS; CORTICAL INTERNEURONS; DIRECTED DIFFERENTIATION; GABAERGIC INTERNEURONS; FUNCTIONAL MATURATION; GLUTAMATERGIC NEURONS; TANGENTIAL MIGRATION; SELF-ORGANIZATION; IN-VITRO; EXPRESSION;
D O I
10.1038/nmeth.4304
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Human brain development involves complex interactions between different regions, including long-distance neuronal migration or formation of major axonal tracts. Different brain regions can be cultured in vitro within 3D cerebral organoids, but the random arrangement of regional identities limits the reliable analysis of complex phenotypes. Here, we describe a coculture method combining brain regions of choice within one organoid tissue. By fusing organoids of dorsal and ventral forebrain identities, we generate a dorsal-ventral axis. Using fluorescent reporters, we demonstrate CXCR4-dependent GABAergic interneuron migration from ventral to dorsal forebrain and describe methodology for time-lapse imaging of human interneuron migration. Our results demonstrate that cerebral organoid fusion cultures can model complex interactions between different brain regions. Combined with reprogramming technology, fusions should offer researchers the possibility to analyze complex neurodevelopmental defects using cells from neurological disease patients and to test potential therapeutic compounds.
引用
收藏
页码:743 / +
页数:12
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