Human neural tube morphogenesis in vitro by geometric constraints.
Human neural tube morphogenesis in vitro by geometric constraints.
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DOI：
10.1038/s41586-021-04026-9
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发表时间：
2021-11
期刊：
影响因子：
64.8
通讯作者：
Streichan SJ
中科院分区：
文献类型：
--
作者：
Karzbrun E;Khankhel AH;Megale HC;Glasauer SMK;Wyle Y;Britton G;Warmflash A;Kosik KS;Siggia ED;Shraiman BI;Streichan SJ
了解人体器官的形成是具有强烈医学影响的科学挑战。三维干细胞培养物为人类细胞分化提供了见解。然而，当前的方法使用无脚手架的干细胞聚集体，这些骨料会产生不可再生的组织形状和可变的细胞粘液模式。这限制了他们概括器官形成的能力。在这里，我们提出了一个基于芯片的培养系统，该系统可以使微图案干细胞自组织成精确的三维细胞污染模式和器官形状。我们使用该系统来重现菜肴中人类干细胞折叠的神经管。神经诱导后，神经外胚层折叠成一个毫米长的神经管，覆盖了非神经外胚层。折叠发生在90％的忠诚度，而解剖学上类似于发育中的人类神经管。我们发现，神经和非神经外胚层是必要的，足以折叠形态发生。我们确定了两种驱动折叠的机制：1）神经外胚层的根尖收缩，以及2）通过非神经外胚层通过细胞外基质合成介导的基础粘附。使用阻力靶向这两种机制会导致类似于神经管缺陷的缺陷。最后，我们表明神经组织宽度决定了神经管的形状，表明沿前轴的形态取决于神经外胚层几何，除了分子梯度。我们的方法为研究人体器官的形态发生提供了新的途径。
Understanding human organ formation is a scientific challenge with strong medical implications. Three-dimensional stem cell cultures have provided insights into human cell differentiation. However, current approaches use scaffold-free stem-cell aggregates, which develop unreproducible 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 induction, neural ectoderm folds into a millimeter 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 drags leads to deficits similar to neural tube defects. Finally, we show that neural tissue width determines neural tube shape, suggesting morphology along the anterior posterior axis depends on neural ectoderm geometry in addition to molecular gradients. Our approach provides a new path to study human organ morphogenesis in health and disease.
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影响因子：
2.6
作者：
Hughes A;Greene NDE;Copp AJ;Galea GL
通讯作者：
Galea GL
影响因子：
4.6
作者：
Britton, George;Heemskerk, Idse;Warmflash, Aryeh
通讯作者：
Warmflash, Aryeh
影响因子：
7.7
作者：
Rolo A;Savery D;Escuin S;de Castro SC;Armer HE;Munro PM;Molè MA;Greene ND;Copp AJ
通讯作者：
Copp AJ
影响因子：
3.7
作者：
Baldassarre M;Razinia Z;Burande CF;Lamsoul I;Lutz PG;Calderwood DA
通讯作者：
Calderwood DA
DOI：
10.1002/advs.202001100
发表时间：
2021-03
期刊：
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子：
--
作者：
Sahni G;Chang SY;Meng JTC;Tan JZY;Fatien JJC;Bonnard C;Utami KH;Chan PW;Tan TT;Altunoglu U;Kayserili H;Pouladi M;Reversade B;Toh YC
通讯作者：
Toh YC