小柯机器人

美国加州大学圣巴巴拉分校Sebastian J. Streichan、Eyal Karzbrun等研究人员合作实现几何约束下的体外人神经管形态发生。相关论文于2021年10月27日在线发表于国际学术期刊《自然》。

研究人员提出了一个基于芯片的培养系统，使干细胞自我组织成精确的三维细胞命运模式和器官形状。研究人员用这个系统在一个培养皿里从人类干细胞中重现神经管的折叠。神经诱导后，神经外胚层折叠成一毫米长的神经管，上面覆盖着非神经外胚层。折叠的保真度为90%，在解剖学上类似于发育中的人类神经管。研究人员发现，神经和非神经外胚层对于折叠的形态发生是必要和充分的。

研究人员发现有两种机制驱动折叠。(1）神经外胚层的顶端收缩，和（2）通过非神经外胚层的细胞外基质合成介导的基底粘附。用药物靶向这两种机制会导致类似于神经管缺陷的形态学缺陷。最后，研究人员表明，神经组织的宽度决定了神经管的形状，这表明沿前后轴的形态除了取决于分子梯度外，还取决于神经外胚层的几何结构。这个方法为研究健康和疾病中的人类器官形态发生提供了一条新途径。

据介绍，了解人类器官的形成是一项科学挑战，具有深远的医学意义。三维干细胞培养提供了对人类细胞分化的见解。然而，目前的方法是使用无支架的干细胞聚集体，它们形成不可复制的组织形状和可变的细胞命运模式。这限制了他们再现器官形成的能力。

附：英文原文

Title: Human neural tube morphogenesis in vitro by geometric constraints

Author: Karzbrun, Eyal, Khankhel, Aimal H., Megale, Heitor C., Glasauer, Stella M. K., Wyle, Yofiel, Britton, George, Warmflash, Aryeh, Kosik, Kenneth S., Siggia, Eric D., Shraiman, Boris I., Streichan, Sebastian J.

Issue&Volume: 2021-10-27

Abstract: Understanding human organ formation is a scientific challenge with far-reaching medical implications1,2. Three-dimensional stem-cell cultures have provided insights into human cell differentiation3,4. However, current approaches use scaffold-free stem-cell aggregates, which develop non-reproducible tissue shapes and variable cell-fate patterns. This limits their capacity to recapitulate organ formation. Here we present a chip-based culture system that enables self-organization of micropatterned stem cells into precise three-dimensional cell-fate patterns and organ shapes. We use this system to recreate neural tube folding from human stem cells in a dish. Upon neural induction5,6, neural ectoderm folds into a millimetre-long neural tube covered with non-neural ectoderm. Folding occurs at 90% fidelity, and anatomically resembles the developing human neural tube. We find that neural and non-neural ectoderm are necessary and sufficient for folding morphogenesis. We identify two mechanisms drive folding: (1) apical contraction of neural ectoderm, and (2) basal adhesion mediated via extracellular matrix synthesis by non-neural ectoderm. Targeting these two mechanisms using drugs leads to morphological defects similar to neural tube defects. Finally, we show that neural tissue width determines neural tube shape, suggesting that morphology along the anterior–posterior axis depends on neural ectoderm geometry in addition to molecular gradients7. Our approach provides a new route to the study of human organ morphogenesis in health and disease.

DOI: 10.1038/s41586-021-04026-9

Source: https://www.nature.com/articles/s41586-021-04026-9

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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