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Temporal Modulations of NODAL, BMP, and WNT Signals Guide the Spatial Patterning in Self-Organized Human Ectoderm Tissues
Matter ( IF 18.9 ) Pub Date : 2020-05-08 , DOI: 10.1016/j.matt.2020.04.012
Tianfa Xie , Jiming Kang , ChangHui Pak , Hongyan Yuan , Yubing Sun

Developmental biology studies using model organisms suggest that the emergence of spatial patterning in the ectoderm is mediated by the morphogen gradients. However, it is still unclear whether the morphogen gradient is necessary and dominates the cell spatial patterning, particularly in human genetic background. Here, we demonstrate that human pluripotent stem cells can self-organize to concentric rings of all major cell types in ectoderm when cultured on micropatterned surfaces in a chemically defined condition. We reveal that modulating the dynamics of NODAL, BMP, and WNT signals is sufficient to control the spatial order of different cell types. Our mathematical model suggests that changes in wavelength and phase of signaling patterns formed via reaction-diffusion may be the mechanism by which temporal information is translated into spatial information. Together, our work demonstrates that in vitro human ectoderm microtissues have great potential in understanding the mechanisms of early-stage human development.



中文翻译:

NODAL,BMP和WNT信号的时间调制指导自组织人类外胚层组织中的空间格局。

使用模型生物的发育生物学研究表明,外胚层中空间形态的出现是由形态发生子梯度介导的。然而,尚不清楚吗啡梯度是否是必要的并且是否主导了细胞的空间模式,特别是在人类遗传背景下。在这里,我们证明了人类多能干细胞在化学定义的条件下在微模式表面上培养时,可以自组织成外胚层中所有主要细胞类型的同心环。我们发现,调节NODAL,BMP和WNT信号的动力学足以控制不同细胞类型的空间顺序。我们的数学模型表明,通过反应扩散形成的信号模式的波长和相位变化可能是时间信息转化为空间信息的机制。在一起,我们的工作表明体外人类外胚层微组织在理解人类早期发育的机制方面具有巨大潜力。

更新日期:2020-05-08
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