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Modeling neural tube development by differentiation of human embryonic stem cells in a microfluidic WNT gradient

Rifes, Pedro LU ; Isaksson, Marc LU ; Rathore, Gaurav Singh ; Aldrin-Kirk, Patrick LU ; Møller, Oliver Knights ; Barzaghi, Guido ; Lee, Julie ; Egerod, Kristoffer Lihme ; Rausch, Dylan M. and Parmar, Malin LU orcid , et al. (2020) In Nature Biotechnology 38(11). p.1265-1273
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... (More)

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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publishing date
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Contribution to journal
publication status
published
subject
in
Nature Biotechnology
volume
38
issue
11
pages
9 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:32451506
  • scopus:85085318079
ISSN
1087-0156
DOI
10.1038/s41587-020-0525-0
language
English
LU publication?
yes
id
b366f017-3b97-40fe-93eb-74a26a2ce29d
date added to LUP
2020-06-26 10:26:13
date last changed
2024-11-01 06:51:55
@article{b366f017-3b97-40fe-93eb-74a26a2ce29d,
  abstract     = {{<p>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.</p>}},
  author       = {{Rifes, Pedro and Isaksson, Marc and Rathore, Gaurav Singh and Aldrin-Kirk, Patrick and Møller, Oliver Knights and Barzaghi, Guido and Lee, Julie and Egerod, Kristoffer Lihme and Rausch, Dylan M. and Parmar, Malin and Pers, Tune H. and Laurell, Thomas and Kirkeby, Agnete}},
  issn         = {{1087-0156}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{1265--1273}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Biotechnology}},
  title        = {{Modeling neural tube development by differentiation of human embryonic stem cells in a microfluidic WNT gradient}},
  url          = {{http://dx.doi.org/10.1038/s41587-020-0525-0}},
  doi          = {{10.1038/s41587-020-0525-0}},
  volume       = {{38}},
  year         = {{2020}},
}