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科学家建立体外神经管发育模型
作者:小柯机器人 发布时间:2020/5/27 15:40:32

丹麦哥本哈根大学Agnete Kirkeby团队通过微流控WNT梯度诱导人类胚胎干细胞分化,实现神经管发育建模。相关论文于2020年5月25日在线发表在《自然—生物技术》杂志上。

研究人员使用在微流控设备中培养的人类胚胎干细胞对人类神经管的早期发育进行建模。该方法称为微流控干细胞区域化(MiSTR),可将多能干细胞暴露于模拟发育模式的信号梯度中。使用WNT激活梯度,研究人员生成了一个神经组织,其表现出从前脑到中脑再到后脑的渐进分化,包括形成峡组织特征。

单细胞转录组学显示,在分化的24小时已经建立了组织,并且神经特异性转录程序的第一个标志物出现在了48小时的细胞中。组织分化的转录组特征概括了小鼠胚胎中早期神经板的基因表达模式。因此,MiSTR将促进对神经管分化因子和过程的研究。

据了解,缺乏组织样本和合适的体外模型限制了人类大脑发育的研究。

附:英文原文

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

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

Issue&Volume: 2020-05-25

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 24h of differentiation, and that the first markers of a neural-specific transcription program emerged in the rostral cells at 48h. 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.

DOI: 10.1038/s41587-020-0525-0

Source: https://www.nature.com/articles/s41587-020-0525-0

期刊信息

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:31.864
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex