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Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids

机译：小鼠胚胎干细胞转化为胃泌素的多轴自组织特性

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摘要

The emergence of multiple axes is an essential element in the establishment of the mammalian body plan. This process takes place shortly after implantation of the embryo within the uterus and relies on the activity of gene regulatory networks that coordinate transcription in space and time. Whereas genetic approaches have revealed important aspects of these processes~(1), a mechanistic understanding is hampered by the poor experimental accessibility of early post-implantation stages. Here we show that small aggregates of mouse embryonic stem cells (ESCs), when stimulated to undergo gastrulation-like events and elongation in vitro, can organize a post-occipital pattern of neural, mesodermal and endodermal derivatives that mimic embryonic spatial and temporal gene expression. The establishment of the three major body axes in these 'gastruloids'~(2,3)suggests that the mechanisms involved are interdependent. Specifically, gastruloids display the hallmarks of axial gene regulatory systems as exemplified by the implementation of collinear Hox transcriptional patterns along an extending antero-posterior axis. These results reveal an unanticipated self-organizing capacity of aggregated ESCs and suggest that gastruloids could be used as a complementary system to study early developmental events in the mammalian embryo.
机译：多轴的出现是建立哺乳动物身体计划的基本要素。此过程发生在胚胎植入子宫后不久，并依赖于协调时空转录的基因调控网络的活性。尽管遗传学方法揭示了这些过程的重要方面〜（1），但由于早期植入后阶段较差的实验可及性，妨碍了机械学的理解。在这里我们表明，小鼠胚胎干细胞（ESCs）的小聚集体在被刺激后会经历类似胃消化的事件并在体外伸长时，可以组织出模仿胚胎时空基因表达的神经，中胚层和内胚层衍生物的枕后模式。 。这些“类胃激素”〜（2,3）中三个主要身体轴的建立表明所涉及的机制是相互依赖的。具体来说，类固醇显示轴向基因调控系统的标志，例如通过沿延伸的前后轴共线Hox转录模式的实现举例说明。这些结果揭示了聚集的ESC出乎意料的自组织能力，并暗示了类固醇可以用作研究哺乳动物胚胎早期发育事件的补充系统。

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  • 来源
    《Nature》 |2018年第7726期|272-276|共5页
  • 作者

    Leonardo Beccari; Naomi Moris; Mehmet Girgin; David A Turner; Peter Baillie-Johnson; Anne-Catherine Cossy; Matthias P Lutolf; Denis Duboule; Alfonso Martinez Arias;

  • 作者单位

    Department of Genetics and Evolution, University of Geneva, Geneva, Switzerland;

    Department of Genetics, University of Cambridge, Cambridge, UK;

    School of Life Sciences, Federal Institute of Technology EPFL, Lausanne, Switzerland;

    Department of Genetics, University of Cambridge, Cambridge, UK;

    Department of Genetics, University of Cambridge, Cambridge, UK,Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK;

    Swiss Cancer Research Institute (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland;

    School of Life Sciences, Federal Institute of Technology EPFL, Lausanne, Switzerland;

    Department of Genetics and Evolution, University of Geneva, Geneva, Switzerland,Swiss Cancer Research Institute (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland;

    Department of Genetics, University of Cambridge, Cambridge, UK;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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