美国密歇根大学医学院Jianping Fu及其研究组研发出基于微流控梯度的人类神经管（NT）模型。这一研究成果发表在2024年2月26日出版的国际学术期刊《自然》上。

研究人员建立了一种基于人类多能干细胞（hPSC）的微流控NT样结构（或μNTLS），它的发育再现了大脑和脊髓（SC）区域以及R-C和D-V轴神经模式化的关键过程。研究利用μNTLS研究了神经细胞系的发育，揭示了神经嵴（NC）祖细胞轴向特化的预模式化，以及神经表皮祖细胞（NMPs）和尾部基因CDX2在SC和躯干NC发育中的功能。

研究人员进一步建立了D-V模式的微流控前脑样结构（μFBLS），其背侧和腹侧区域在空间上相互分离，顶基底细胞组织分层，分别模拟了人类前脑allium和subpallium的发育过程。μNTLS和μFBLS共同揭示了三维腔隙的组织结构，具有与活体类似的时空细胞分化和组织结构，其有望用于研究人类神经发育和疾病病理。

据介绍，人类神经系统可以说是最复杂却又高度组织化的器官。其复杂性和组织性是在人神经系统的胚胎前体-神经管区域模式化过程中形成的。一直以来，对神经管模式化的研究都依赖于动物模型。最近，基于hPSC的神经发育模型（包括神经器官组织和生物工程NT发育模型）悄然兴起。然而，现有的基于hPSC的模型未能在三维（3D）管状几何中再现沿喙-尾（R-C）轴和背-腹（D-V）轴的神经模式化，而这正是NT发育的标志。

附：英文原文

Title: A Patterned Human Neural Tube Model Using Microfluidic Gradients

Author: Xue, Xufeng, Kim, Yung Su, Ponce-Arias, Alfredo-Isaac, OLaughlin, Richard, Yan, Robin Zhexuan, Kobayashi, Norio, Tshuva, Rami Yair, Tsai, Yu-Hwai, Sun, Shiyu, Zheng, Yi, Liu, Yue, Wong, Frederick C. K., Surani, Azim, Spence, Jason R., Song, Hongjun, Ming, Guo-Li, Reiner, Orly, Fu, Jianping

Issue&Volume: 2024-02-26

Abstract: Human nervous system is arguably the most complex but highly organized organ. Foundation of its complexity and organization is laid down during regional patterning of neural tube (NT), the embryonic precursor to human nervous system. Historically, studies of NT patterning have relied on animal models to uncover underlying principles. Recently, human pluripotent stem cell (hPSC)-based models of neurodevelopment, including neural organoids1-5 and bioengineered NT development models6-10, are emerging. However, existing hPSC-based models fail to recapitulate neural patterning along both rostral-caudal (R-C) and dorsal-ventral (D-V) axes in a three-dimensional (3D) tubular geometry, a hallmark of NT development. Herein we report a hPSC-based, microfluidic NT-like structure (or μNTLS), whose development recapitulates some critical aspects of neural patterning in both brain and spinal cord (SC) regions and along both R-C and D-V axes. The μNTLS was utilized for studying neuronal lineage development, revealing prepatterning of axial identities of neural crest (NC) progenitors and functional roles of neuromesodermal progenitors (NMPs) and caudal gene CDX2 in SC and trunk NC development. We further developed D-V patterned, microfluidic forebrain-like structures (μFBLS) with spatially segregated dorsal and ventral regions and layered apicobasal cellular organizations that mimic human forebrain pallium and subpallium developments, respectively. Together, both μNTLS and μFBLS offer 3D lumenal tissue architectures with an in vivo-like spatiotemporal cell differentiation and organization, promising for studying human neurodevelopment and disease.

DOI: 10.1038/s41586-024-07204-7

Source: https://www.nature.com/articles/s41586-024-07204-7

期刊信息

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

官方网址：http://www.nature.com

投稿链接：http://www.nature.com/authors/submit_manuscript.html