A patterned human neural tube model using microfluidic gradients.
A patterned human neural tube model using microfluidic gradients.
复制标题
使用微流体梯度的图案化人类神经管模型。
DOI：
10.1038/s41586-024-07204-7
复制
发表时间：
2024
期刊：
影响因子：
64.8
通讯作者：
Ming,G
中科院分区：
文献类型：
--
作者：
Xue,Xufeng;Kim,YungSu;Ponce-Arias,Alfredo-Isaac;O'Laughlin,Richard;Yan,RobinZhexuan;Kobayashi,Norio;Tshuva,RamiYair;Tsai,Yu-Hwai;Sun,Shiyu;Zheng,Yi;Liu,Yue;Wong,FrederickCK;Surani,Azim;Spence,JasonR;Song,Hongjun;Ming,G
人类的神经系统是一个高度复杂但有组织的器官。它的复杂性和组织的基础是在神经管的区域模式化过程中奠定的，神经管是人类神经系统的胚胎前体。从历史上看，神经管模式的研究依赖于动物模型来揭示潜在的原理。最近，出现了基于人类多能干细胞的神经发育模型，包括神经类器官、、-和生物工程神经管发育模型、、-。然而，这样的模型未能概括神经图案沿着在一个三维管状几何形状，神经管发育的标志，沿头尾和背腹轴。在这里，我们报告了一个人类多能干细胞为基础的，微流体神经管样结构，它的发展概括了几个关键方面的神经模式在大脑和脊髓区域和沿着喙尾和背腹轴。该结构被用于研究神经元谱系发育，其揭示了神经嵴祖细胞的轴向身份的预图案化以及神经中胚层祖细胞和尾部基因CDX 2在脊髓和躯干神经嵴发育中的功能作用。我们进一步开发了背腹图案的微流体前脑样结构与空间隔离的背侧和腹侧区域和分层apicobasal细胞组织，分别模仿人类前脑腭和腭下的发展。这些基于微流体的神经发育模型共同提供了具有体内时空细胞分化和组织的三维腔内组织架构，这将促进人类神经发育和疾病的研究。
The human nervous system is a highly complex but organized organ. The foundation of its complexity and organization is laid down during regional patterning of the neural tube, the embryonic precursor to the human nervous system. Historically, studies of neural tube patterning have relied on animal models to uncover underlying principles. Recently, models of neurodevelopment based on human pluripotent stem cells, including neural organoids, , , –and bioengineered neural tube development models, , , –, have emerged. However, such models fail to recapitulate neural patterning along both rostral–caudal and dorsal–ventral axes in a three-dimensional tubular geometry, a hallmark of neural tube development. Here we report a human pluripotent stem cell-based, microfluidic neural tube-like structure, the development of which recapitulates several crucial aspects of neural patterning in brain and spinal cord regions and along rostral–caudal and dorsal–ventral axes. This structure was utilized for studying neuronal lineage development, which revealed pre-patterning of axial identities of neural crest progenitors and functional roles of neuromesodermal progenitors and the caudal geneCDX2in spinal cord and trunk neural crest development. We further developed dorsal–ventral patterned microfluidic forebrain-like structures with spatially segregated dorsal and ventral regions and layered apicobasal cellular organizations that mimic development of the human forebrain pallium and subpallium, respectively. Together, these microfluidics-based neurodevelopment models provide three-dimensional lumenal tissue architectures with in vivo-like spatiotemporal cell differentiation and organization, which will facilitate the study of human neurodevelopment and disease.