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| Status |
Public on May 25, 2020 |
| Title |
Modelling rostro-caudal neural tube regionalization from human embryonic stem cells with a microfluidic morphogenic gradient |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Studies in animal models have been fundamental for understanding brain development but only a fraction of these findings have been validated in a human context. Here, we tissue-engineered a model (MiSTR) of human neural tube regionalization based on human embryonic stem cells (hESCs) and microfluidic cell culturing. By exposing differentiating hESCs to a WNT signalling gradient we mimicked early rostro-caudal neural patterning, and with >80% reproducibility generated a coherent tissue with progressive caudalization from forebrain over midbrain to hindbrain, including formation of isthmic organiser characteristics. Single-cell transcriptomics revealed that rostro-caudal organization was established already at 24 hours of differentiation, before expression of neural markers. Moreover, the transcriptomic hallmarks of rostro-caudal MiSTR organization accurately recapitulated gene expression patterns of the early rostro-caudal neural plate in mouse embryos. MiSTR thereby represents a novel in vitro model of human neurodevelopment to deconstruct and systematically analyze factors responsible for rostro-caudal neural tube patterning.
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| Overall design |
Single-cell transcriptomics of an in vitro model of early human neural patterning, at various time points and dorsal and ventral locations.
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| Web link |
https://www.nature.com/articles/s41587-020-0525-0
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| |
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| Contributor(s) |
Rifes P, Isaksson M, Rathore GS, kirk PA, Møller OK, Barzaghi G, Lee J, Egerod KL, Rausch DM, Parmar M, Pers TH, Laurell T, Kirkeby A |
| Citation(s) |
32451506 |
| |
| Submission date |
Aug 05, 2019 |
| Last update date |
Jun 04, 2020 |
| Contact name |
Gaurav Singh Rathore |
| E-mail(s) |
[email protected]
|
| Phone |
50175653
|
| Organization name |
University of Copenhagen
|
| Department |
Department of Neuroscience
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| Lab |
Agnete Kirkeby lab
|
| Street address |
Department of Neuroscience Faculty of Health and Medical Sciences Blegdamsvej 3B, Building 7, 4th floor
|
| City |
Copenhagen |
| ZIP/Postal code |
2200 |
| Country |
Denmark |
| |
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| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA558753 |
| SRA |
SRP217591 |
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