Construction of a mammalian embryo model from stem cells organized by a morphogen signalling centre.
Construction of a mammalian embryo model from stem cells organized by a morphogen signalling centre.
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由形态信号中心组织的干细胞的哺乳动物胚胎模型的构建。
DOI：
10.1038/s41467-021-23653-4
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发表时间：
2021-06-02
影响因子：
16.6
通讯作者：
Thisse C
中科院分区：
文献类型：
--
作者：
Xu PF;Borges RM;Fillatre J;de Oliveira-Melo M;Cheng T;Thisse B;Thisse C
从多能干细胞体外产生适当分化的胚胎结构仍然是一个挑战。在这里，我们表明，指令的小鼠胚胎干细胞与实验工程的形态发生信号中心，作为一个组织者的功能，在胚胎样实体（胚状体）的发展结果。原位杂交、免疫标记、细胞追踪和转录组学分析表明，这些胚状体通过原肠胚形成过程形成三个胚层，并且它们表现出广泛的发育结构，与神经胚阶段的小鼠胚胎高度相似。胚状体围绕轴索中胚层组织，具有背侧神经板，其显示类似于鼠胚胎神经上皮的组织学特性，并且从后中脑到尾尖折叠成前后图案的神经管。在脊索中胚层的侧面，胚状体具有体节和中间中胚层，心脏组织向前跳动，并形成血管网。胚胎分化出一个原始的肠管，其前后和背腹都有图案。总之，胚状体提供了一种哺乳动物胚胎的体外模型，显示了胚层衍生物的广泛发育，并有望成为体外研究和疾病建模的有力工具。根据形态发生分泌中心的指示，小鼠胚胎干细胞的聚集体发育成围绕轴向中胚层组织的胚胎样结构，其显示出神经元期小鼠胚胎的广泛特征，具有胚层衍生物的前后和背腹图案。
Generating properly differentiated embryonic structures in vitro from pluripotent stem cells remains a challenge. Here we show that instruction of aggregates of mouse embryonic stem cells with an experimentally engineered morphogen signalling centre, that functions as an organizer, results in the development of embryo-like entities (embryoids). In situ hybridization, immunolabelling, cell tracking and transcriptomic analyses show that these embryoids form the three germ layers through a gastrulation process and that they exhibit a wide range of developmental structures, highly similar to neurula-stage mouse embryos. Embryoids are organized around an axial chordamesoderm, with a dorsal neural plate that displays histological properties similar to the murine embryo neuroepithelium and that folds into a neural tube patterned antero-posteriorly from the posterior midbrain to the tip of the tail. Lateral to the chordamesoderm, embryoids display somitic and intermediate mesoderm, with beating cardiac tissue anteriorly and formation of a vasculature network. Ventrally, embryoids differentiate a primitive gut tube, which is patterned both antero-posteriorly and dorso-ventrally. Altogether, embryoids provide an in vitro model of mammalian embryo that displays extensive development of germ layer derivatives and that promises to be a powerful tool for in vitro studies and disease modelling. Following instruction by a morphogen secreting centre, aggregates of mouse embryonic stem cells develop into embryo-like structures organized around an axial mesoderm, which show extensive characteristics of a neurula-stage mouse embryo, with antero-posterior and dorso-ventral patterning of germ layer derivatives.
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DOI：
10.1073/pnas.1734197100
发表时间：
2003-09-30
影响因子：
11.1
作者：
Aubert, J;Stavridis, MP;Smith, A
通讯作者：
Smith, A
影响因子：
2.6
作者：
Grimmond, S;Larder, R;Greenfield, A
通讯作者：
Greenfield, A
影响因子：
4.6
作者：
Grego-Bessa, Joaquim;Hildebrand, Jeffrey;Anderson, Kathryn V.
通讯作者：
Anderson, Kathryn V.
影响因子：
3.9
作者：
Hadjantonakist, Anna-Katerina;Siggia, Eric D.;Simunovic, Mijo
通讯作者：
Simunovic, Mijo
影响因子：
11.8
作者：
Ben-Haim, Nadav;Lu, Cindy;Constam, Daniel B.
通讯作者：
Constam, Daniel B.