Gastruloids generated without exogenous Wnt activation develop anterior neural tissues.
Gastruloids generated without exogenous Wnt activation develop anterior neural tissues.
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DOI：
10.1016/j.stemcr.2021.03.017
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发表时间：
2021-05-11
影响因子：
5.9
通讯作者：
Lutolf MP
中科院分区：
文献类型：
--
作者：
Girgin MU;Broguiere N;Mattolini L;Lutolf MP
当用来自外源性WNT通路激活剂的脉冲刺激时，小鼠胚胎干细胞（ESC）的小聚集体可以经历胚胎样轴向形态发生和沿沿着三个主要身体轴的图案化。然而，这些被称为胃状体的结构目前缺乏前胚胎区域，例如属于大脑的区域。在这里，我们描述了一种方法来生成具有更完整的前后发展的类胃。我们使用水凝胶微孔阵列以可重复和可扩展的方式促进小鼠ESC稳健地衍生为植入后外胚层样（EPI）聚集体。这些EPI聚集体在没有外部化学刺激的情况下打破对称性并轴向伸长。在发育的早期阶段抑制WNT信号传导导致具有前部神经组织的类胃体的形成。因此，我们提供了一个新的工具，在体外研究植入后的小鼠的发展，特别是前神经区的形成。小鼠胚胎干细胞可以聚集形成外胚层样（EPI）聚集体EPI聚集体在没有外源性WNT激活的情况下经历轴向形态发生初始聚集体大小是轴向形态发生的主要决定因素早期WNT抑制对于前神经祖细胞的出现是必不可少的。在这篇文章中，Lutolf及其同事提出了一种新的方法来研究体外植入后胚胎发育。小鼠胚胎干细胞的聚集体显示出分化成具有胚胎样图案和形态发生的结构。此外，初始聚集体的大小和Wnt信号的抑制已被证明是至关重要的轴向形态发生和出现的前神经祖细胞。
When stimulated with a pulse from an exogenous WNT pathway activator, small aggregates of mouse embryonic stem cells (ESCs) can undergo embryo-like axial morphogenesis and patterning along the three major body axes. However, these structures, called gastruloids, currently lack the anterior embryonic regions, such as those belonging to the brain. Here, we describe an approach to generate gastruloids that have a more complete antero-posterior development. We used hydrogel microwell arrays to promote the robust derivation of mouse ESCs into post-implantation epiblast-like (EPI) aggregates in a reproducible and scalable manner. These EPI aggregates break symmetry and axially elongate without external chemical stimulation. Inhibition of WNT signaling in early stages of development leads to the formation of gastruloids with anterior neural tissues. Thus, we provide a new tool to study the development of the mouse after implantation in vitro, especially the formation of anterior neural regions. Mouse embryonic stem cells can be aggregated to form epiblast-like (EPI) aggregates EPI aggregates undergo axial morphogenesis in the absence of exogenous WNT activation Initial aggregate size is a major determinant for axial morphogenesis Early WNT inhibition is essential for the emergence of anterior neural progenitors In this article, Lutolf and colleagues propose a new method to study post-implantation embryonic development in vitro. Aggregates of mouse embryonic stem cells were shown to differentiate into structures with embryo-like patterning and morphogenesis. Furthermore, initial aggregate size and inhibition of Wnt signaling has been shown to be crucial for the axial morphogenesis and emergence of anterior neural progenitors.
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影响因子：
4.3
作者：
Serup P;Gustavsen C;Klein T;Potter LA;Lin R;Mullapudi N;Wandzioch E;Hines A;Davis A;Bruun C;Engberg N;Petersen DR;Peterslund JM;Macdonald RJ;Grapin-Botton A;Magnuson MA;Zaret KS
通讯作者：
Zaret KS
DOI：
10.1242/dev.085654
发表时间：
2013-03
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Faunes F;Hayward P;Descalzo SM;Chatterjee SS;Balayo T;Trott J;Christoforou A;Ferrer-Vaquer A;Hadjantonakis AK;Dasgupta R;Arias AM
通讯作者：
Arias AM
影响因子：
4.6
作者：
Ghimire S;Van der Jeught M;Neupane J;Roost MS;Anckaert J;Popovic M;Van Nieuwerburgh F;Mestdagh P;Vandesompele J;Deforce D;Menten B;Chuva de Sousa Lopes S;De Sutter P;Heindryckx B
通讯作者：
Heindryckx B
影响因子：
4.6
作者：
Lewis, Samara L.;Khoo, Poh-Lynn;Tam, Patrick P. L.
通讯作者：
Tam, Patrick P. L.
影响因子：
2.7
作者：
BAIN, G;KITCHENS, D;GOTTLIEB, DI
通讯作者：
GOTTLIEB, DI