Mouse ICM Organoids Reveal Three-Dimensional Cell Fate Clustering
Mouse ICM Organoids Reveal Three-Dimensional Cell Fate Clustering
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DOI：
10.1016/j.bpj.2018.11.011
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发表时间：
2019-01-08
影响因子：
3.4
通讯作者：
Fischer, Sabine C.
中科院分区：
文献类型：
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作者：
Mathew, Biena;Munoz-Descalzo, Silvia;Fischer, Sabine C.
在哺乳动物植入前，内细胞团（ICM）的细胞采用胚胎或胚外的命运。这一过程在空间和时间上受到严格调控，先前已在小鼠胚胎和胚胎干细胞模型中进行了研究。目前的研究表明，细胞的命运是安排在一个盐和胡椒图案的随机细胞定位或空间交替模式。然而，细胞命运规格的三维模式的细节还没有在胚胎中，也没有在体外系统中进行研究。据我们所知，我们开发了ICM类器官作为一种新型三维体外干细胞系统，以模拟ICM中发生的命运决定机制。ICM类器官显示出与体内系统的相似性，无论几何形状和总细胞数的差异如何。检查ICM类器官和小鼠胚胎，我们描述了一个迄今为止未知的局部聚类的细胞在这两个系统中具有相同的命运。这些发现是基于三维定量分析的时空模式的NANOG和GATA 6的表达结合计算规则为基础的建模。我们的分析所确定的模式与目前盐和胡椒模式的观点不同。我们的调查的空间分布在体内和体外解剖胚胎的不同部分的细胞命运规格的贡献。从长远来看，我们的定量体内和体外分析的组合可以扩展到其他哺乳动物生物体，从而创建一个强大的方法来研究胚胎发生。
During mammalian preimplantation, cells of the inner cell mass (ICM) adopt either an embryonic or an extraembryonic fate. This process is tightly regulated in space and time and has been studied previously in mouse embryos and embryonic stem cell models. Current research suggests that cell fates are arranged in a salt-and-pepper pattern of random cell positioning or a spatially alternating pattern. However, the details of the three-dimensional patterns of cell fate specification have not been investigated in the embryo nor in in vitro systems. We developed ICM organoids as a, to our knowledge, novel three-dimensional in vitro stem cell system to model mechanisms of fate decisions that occur in the ICM. ICM organoids show similarities to the in vivo system that arise regardless of the differences in geometry and total cell number. Inspecting ICM organoids and mouse embryos, we describe a so far unknown local clustering of cells with identical fates in both systems. These findings are based on the three-dimensional quantitative analysis of spatiotemporal patterns of NANOG and GATA6 expression in combination with computational rule-based modeling. The pattern identified by our analysis is distinct from the current view of a salt-and-pepper pattern. Our investigation of the spatial distributions both in vivo and in vitro dissects the contributions of the different parts of the embryo to cell fate specifications. In perspective, our combination of quantitative in vivo and in vitro analyses can be extended to other mammalian organisms and thus creates a powerful approach to study embryogenesis.