胚胎干细胞
神经管
前脑
神经发育
Wnt信号通路
细胞生物学
神经板
诱导多能干细胞
干细胞
神经上皮细胞
定向微分
神经细胞
器官发生
转录组
神经干细胞
生物
胚胎
神经科学
细胞
基因表达
遗传学
基因
中枢神经系统
信号转导
作者
Pedro Rifes,Marc Isaksson,Gaurav Rathore,Patrick Aldrin-Kirk,Oliver Knights Møller,Guido Barzaghi,Julie Lee,Kristoffer L. Egerod,Dylan M. Rausch,Malin Parmar,Tune H. Pers,Thomas Laurell,Agnete Kirkeby
标识
DOI:10.1038/s41587-020-0525-0
摘要
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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