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

by Barzaghi, Guido , Egerod, Kristoffer Lihme , Rathore, Gaurav Singh , Isaksson, Marc , Parmar, Malin , Lee, Julie , Kirkeby, Agnete , Møller, Oliver Knights , Pers, Tune H. , Laurell, Thomas , Rausch, Dylan M. , Rifes, Pedro , Aldrin-Kirk, Patrick

in 631/136/756/1446 / 631/378/2571/2575 / 631/532/1360 / 631/532/2117 / 631/61/2320 / Agriculture / Basic Medicine / Bioinformatics / Biologi / Biological Sciences / Biomedical and Life Sciences / Biomedical Engineering/Biotechnology / Biomedical microelectromechanical systems / Biomedicine / Biotechnology / Body Patterning / Cell and Molecular Biology / Cell Differentiation / Cell- och molekylärbiologi / Cells, Cultured / Comparative analysis / Developmental Biology / Embryo cells / Embryogenesis / Embryonic stem cells / Embryos / Forebrain / Gene expression / Gene Expression Regulation, Developmental / Hindbrain / Human Embryonic Stem Cells - cytology / Humans / Letter / Life Sciences / Medical and Health Sciences / Medicin och hälsovetenskap / Medicinska och farmaceutiska grundvetenskaper / Mesencephalon / Microfluidic devices / Microfluidics / Microfluidics - methods / Natural Sciences / Naturvetenskap / Neural plate / Neural tube / Neural Tube - embryology / Neurulation / Pattern formation / Pluripotency / Single-Cell Analysis / Stem cell transplantation / Stem cells / Transcription / Transcriptome - genetics / Utvecklingsbiologi / Wnt protein / Wnt proteins / Wnt Proteins - metabolism / Wnt Signaling Pathway

2020

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

2020

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2020

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Journal Article

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

Barzaghi, Guido,

Egerod, Kristoffer Lihme,

Rathore, Gaurav Singh,

Isaksson, Marc,

Parmar, Malin,

Lee, Julie,

Kirkeby, Agnete,

Møller, Oliver Knights,

Pers, Tune H.,

Laurell, Thomas,

Rausch, Dylan M.,

Rifes, Pedro,

Aldrin-Kirk, Patrick

2020

Overview

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. Patterning of the human neural tube is modeled in a microfluidic device.

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