Dorsal-ventral patterned neural cyst from human pluripotent stem cells in a neurogenic niche
Dorsal-ventral patterned neural cyst from human pluripotent stem cells in a neurogenic niche
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DOI：
10.1126/sciadv.aax5933
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发表时间：
2019-12
期刊：
影响因子：
13.6
通讯作者：
Y. Zheng;X. Xue;A. M. Resto-Irizarry;Z. Li;Y. Shao;Y. Zheng;G. Zhao;J. Fu
中科院分区：
文献类型：
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作者：
Y. Zheng;X. Xue;A. M. Resto-Irizarry;Z. Li;Y. Shao;Y. Zheng;G. Zhao;J. Fu
利用干细胞建立了具有正常背-腹侧结构的人类神经管发育模型。尽管神经管在中枢神经系统发育中很重要，但由于研究人类胚胎的挑战，以及人类和动物模型之间的发育差异，人类神经管（NT）的发育仍然知之甚少。我们报道了一个人类NT发育模型，其中NT样组织，神经上皮（NE）囊肿，通过人类多能干细胞（hPSCs）的自组织在生物工程神经源性环境中产生。NE囊肿与背外胚层的神经板相对应，具有默认的背侧身份。NE囊肿的背-腹侧（DV）模式是通过维甲酸和/或超音hedgehog基因实现的，其特征是腹底板、P3和pMN结构域在离散的相邻区域连续出现，背侧区域逐渐局限于相反的背极。这种基于hpsc的DV型NE囊肿系统将有助于理解引导NT型的自组织原理，并有助于神经发育和神经疾病的研究。
A human neural tube development model with proper dorsal-ventral patterning is accomplished using stem cells. Despite its importance in central nervous system development, development of the human neural tube (NT) remains poorly understood, given the challenges of studying human embryos, and the developmental divergence between humans and animal models. We report a human NT development model, in which NT-like tissues, neuroepithelial (NE) cysts, are generated in a bioengineered neurogenic environment through self-organization of human pluripotent stem cells (hPSCs). NE cysts correspond to the neural plate in the dorsal ectoderm and have a default dorsal identity. Dorsal-ventral (DV) patterning of NE cysts is achieved using retinoic acid and/or sonic hedgehog and features sequential emergence of the ventral floor plate, P3, and pMN domains in discrete, adjacent regions and a dorsal territory progressively restricted to the opposite dorsal pole. This hPSC-based, DV patterned NE cyst system will be useful for understanding the self-organizing principles that guide NT patterning and for investigations of neural development and neural disease.