A novel self-organizing embryonic stem cell system reveals signaling logic underlying the patterning of human ectoderm
A novel self-organizing embryonic stem cell system reveals signaling logic underlying the patterning of human ectoderm
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DOI：
10.1242/dev.179093
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发表时间：
2019-10-01
期刊：
影响因子：
4.6
通讯作者：
Warmflash, Aryeh
中科院分区：
文献类型：
--
作者：
Britton, George;Heemskerk, Idse;Warmflash, Aryeh
在发育过程中，外胚层通过BMP和WNT信号传导的组合形成模式。模式生物的研究已经为这一过程提供了大量的见解;然而，目前还没有研究人类外胚层模式的系统。此外，神经板边界规范的复杂性使得很难从发现所涉及的基因过渡到更深层次的机制理解。在这里，我们开发了一个体外模型的人外胚层图案，其中人胚胎干细胞自我组织，形成强大的和定量可重复的模式，对应于完整的内侧-外侧轴的胚胎外胚层。使用这个平台，我们表明内源性WNT信号传导的持续时间是一个关键的控制参数，并且细胞在做出命运决定时感知BMP和WNT信号传导的相对水平。这些见解使我们能够开发一种改进的基板分化方案。因此，我们的平台是研究人类外胚层模式和改进定向分化方案的有力工具。
During development, the ectoderm is patterned by a combination of BMP and WNT signaling. Research in model organisms has provided substantial insight into this process; however, there are currently no systems in which to study ectodermal patterning in humans. Further, the complexity of neural plate border specification has made it difficult to transition from discovering the genes involved to deeper mechanistic understanding. Here, we develop an in vitro model of human ectodermal patterning, in which human embryonic stem cells self-organize to form robust and quantitatively reproducible patterns corresponding to the complete medial-lateral axis of the embryonic ectoderm. Using this platform, we show that the duration of endogenous WNT signaling is a crucial control parameter, and that cells sense relative levels of BMP and WNT signaling in making fate decisions. These insights allowed us to develop an improved protocol for placodal differentiation. Thus, our platform is a powerful tool for studying human ectoderm patterning and for improving directed differentiation protocols.This article has an associated 'The people behind the papers' interview.