期刊
NATURE BIOTECHNOLOGY
卷 38, 期 11, 页码 1265-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41587-020-0525-0
关键词
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资金
- Novo Nordisk Foundation [NNF18OC0030286, NNF17CC0027852, NNF18CC0034900]
- Lundbeck Foundation [R190-2014-3904]
- Innovation Fund Denmark [BrainStem 4108-00008 A]
- Strong Research Environment at Lund University Multipark
- Swedish Research Council [70862601/Bagadilico, 521-2012-5624]
- Crafoord Foundation
- Segerfalk Foundation
- Tore Nilsson Foundation
- Sven-Olof Janson Foundation
- Swedish Fund for Research Without Animal Experiments
- New York Stem Cell Foundation
- European Research Council under the ERC Grant Agreement [30971]
Patterning of the human neural tube is modeled in a microfluidic device. The study of brain development in humans is limited by the lack of tissue samples and suitable in vitro models. Here, we model early human neural tube development using human embryonic stem cells cultured in a microfluidic device. The approach, named microfluidic-controlled stem cell regionalization (MiSTR), exposes pluripotent stem cells to signaling gradients that mimic developmental patterning. Using a WNT-activating gradient, we generated a neural tissue exhibiting progressive caudalization from forebrain to midbrain to hindbrain, including formation of isthmic organizer characteristics. Single-cell transcriptomics revealed that rostro-caudal organization was already established at 24 h of differentiation, and that the first markers of a neural-specific transcription program emerged in the rostral cells at 48 h. The transcriptomic hallmarks of rostro-caudal organization recapitulated gene expression patterns of the early rostro-caudal neural plate in mouse embryos. Thus, MiSTR will facilitate research on the factors and processes underlying rostro-caudal neural tube patterning.
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