Modeling neural tube development by differentiation of human embryonic stem cells in a microfluidic WNT gradient
- 25 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Biotechnology
- Vol. 38 (11), 1265-1273
- https://doi.org/10.1038/s41587-020-0525-0
Abstract
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.This publication has 36 references indexed in Scilit:
- Specification of positional identity in forebrain organoidsNature Biotechnology, 2019
- Fused cerebral organoids model interactions between brain regionsNature Methods, 2017
- Assembly of functionally integrated human forebrain spheroidsNature, 2017
- Development-on-chip: in vitro neural tube patterning with a microfluidic deviceDevelopment, 2016
- 3D Reconstitution of the Patterned Neural Tube from Embryonic Stem CellsStem Cell Reports, 2014
- The Role of Organizers in Patterning the Nervous SystemAnnual Review of Neuroscience, 2012
- Generation of Regionally Specified Neural Progenitors and Functional Neurons from Human Embryonic Stem Cells under Defined ConditionsCell Reports, 2012
- Establishing and Interpreting Graded Sonic Hedgehog Signaling during Vertebrate Neural Tube Patterning: The Role of Negative FeedbackCold Spring Harbor Perspectives in Biology, 2009
- Compartments and their boundaries in vertebrate brain developmentNature Reviews Neuroscience, 2005
- Progressive induction of caudal neural character by graded Wnt signalingNature Neuroscience, 2002