Micropattern differentiation of mouse pluripotent stem cells recapitulates embryo regionalized cell fate patterning.
Micropattern differentiation of mouse pluripotent stem cells recapitulates embryo regionalized cell fate patterning.
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DOI：
10.7554/elife.32839
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发表时间：
2018-02-07
期刊：
影响因子：
7.7
通讯作者：
Hadjantonakis AK
中科院分区：
文献类型：
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作者：
Morgani SM;Metzger JJ;Nichols J;Siggia ED;Hadjantonakis AK
在原肠形成过程中，外胚层细胞按照它们所指定的那样具有多能性，并在空间上排列胚胎的三个胚层。类似地，人类多能干细胞(PSC)在微图案化的表面上经历了空间组织的命运规范。由于活体验证对人类是不可能的，我们开发了一种小鼠PSC微模式系统，并通过与小鼠胚胎的直接比较，揭示了不同区域身份的稳健规范。BMP、WNT、激活素和成纤维细胞生长因子引导小鼠上皮样细胞向间充质细胞转变，并呈放射状排列后中胚层的命运。相反，WNT、激活素和成纤维细胞生长因子塑造了包括明确的内胚层在内的前部特征。相比之下，上胚层干细胞是一种发育成熟的状态，只指定了前向身份，但没有模式。小鼠微图案系统提供了一种强大的可扩展的方法来生成存在于体内的区域化细胞类型，解决了信号如何促进不同身份和生成图案的问题，并比较了体内、体外和跨物种的运行机制。
During gastrulation epiblast cells exit pluripotency as they specify and spatially arrange the three germ layers of the embryo. Similarly, human pluripotent stem cells (PSCs) undergo spatially organized fate specification on micropatterned surfaces. Since in vivo validation is not possible for the human, we developed a mouse PSC micropattern system and, with direct comparisons to mouse embryos, reveal the robust specification of distinct regional identities. BMP, WNT, ACTIVIN and FGF directed mouse epiblast-like cells to undergo an epithelial-to-mesenchymal transition and radially pattern posterior mesoderm fates. Conversely, WNT, ACTIVIN and FGF patterned anterior identities, including definitive endoderm. By contrast, epiblast stem cells, a developmentally advanced state, only specified anterior identities, but without patterning. The mouse micropattern system offers a robust scalable method to generate regionalized cell types present in vivo, resolve how signals promote distinct identities and generate patterns, and compare mechanisms operating in vivo and in vitro and across species.