Role of SHH in Patterning Human Pluripotent Cells towards Ventral Forebrain Fates.
Role of SHH in Patterning Human Pluripotent Cells towards Ventral Forebrain Fates.
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SHH在人类多能细胞朝向腹侧前脑命运模式形成中的作用
DOI：
10.3390/cells10040914
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发表时间：
2021-04-16
期刊：
影响因子：
6
通讯作者：
Vaccarino FM
中科院分区：
文献类型：
--
作者：
Brady MV;Vaccarino FM
人类神经发育的复杂性在历史上一直具有挑战性，但在健康神经生物学和疾病的背景下仍然具有很大的兴趣。经典的动物模型和单层体外系统限制了科学家除了技术能力之外可以努力回答的问题类型。然而，三维人类干细胞衍生的类器官系统为模拟人类发育和模仿人体器官的不同细胞组成提供了独特的机会。这种策略具有适应性和延展性，并且这些类神经器官具有形态发生敏感性，可以以各种方式生成人类大脑的不同区域。此外，概括人类发展为疾病建模提供了一个平台。在人类大脑的许多区域，一个主要的人类神经发育调节因子是音猬（SHH），其表达梯度和通路激活负责赋予腹侧身份和塑造整个神经轴的细胞表型。本文首先讨论了使用类器官研究人类神经发育和疾病的益处、挑战和局限性，并比较了与其他体内和体外模型系统的优缺点。接下来，我们将探索SHH对人类神经发育的控制范围，以及SHH在各种干细胞方法（包括类器官）中的应用，以扩大我们对人类发育和疾病的理解。我们概述了这一策略将如何最终使我们更接近于揭示人类神经发育和生物学的复杂性。
The complexities of human neurodevelopment have historically been challenging to decipher but continue to be of great interest in the contexts of healthy neurobiology and disease. The classic animal models and monolayer in vitro systems have limited the types of questions scientists can strive to answer in addition to the technical ability to answer them. However, the tridimensional human stem cell-derived organoid system provides the unique opportunity to model human development and mimic the diverse cellular composition of human organs. This strategy is adaptable and malleable, and these neural organoids possess the morphogenic sensitivity to be patterned in various ways to generate the different regions of the human brain. Furthermore, recapitulating human development provides a platform for disease modeling. One master regulator of human neurodevelopment in many regions of the human brain is sonic hedgehog (SHH), whose expression gradient and pathway activation are responsible for conferring ventral identity and shaping cellular phenotypes throughout the neural axis. This review first discusses the benefits, challenges, and limitations of using organoids for studying human neurodevelopment and disease, comparing advantages and disadvantages with other in vivo and in vitro model systems. Next, we explore the range of control that SHH exhibits on human neurodevelopment, and the application of SHH to various stem cell methodologies, including organoids, to expand our understanding of human development and disease. We outline how this strategy will eventually bring us much closer to uncovering the intricacies of human neurodevelopment and biology.
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影响因子：
16.6
作者：
Eto H;Kishi Y;Yakushiji-Kaminatsui N;Sugishita H;Utsunomiya S;Koseki H;Gotoh Y
通讯作者：
Gotoh Y
影响因子：
5.3
作者：
Cao L;Hu R;Xu T;Zhang ZN;Li W;Lu J
通讯作者：
Lu J
影响因子：
16.6
作者：
Du, Zhong-Wei;Chen, Hong;Liu, Huisheng;Lu, Jianfeng;Qian, Kun;Huang, CindyTzu-Ling;Zhong, Xiaofen;Fan, Frank;Zhang, Su-Chun
通讯作者：
Zhang, Su-Chun
影响因子：
14.5
作者：
Bodi, Nikoletta;Keri, Szabolcs;Gluck, Mark A.
通讯作者：
Gluck, Mark A.
影响因子：
64.8
作者：
Birey F;Andersen J;Makinson CD;Islam S;Wei W;Huber N;Fan HC;Metzler KRC;Panagiotakos G;Thom N;O'Rourke NA;Steinmetz LM;Bernstein JA;Hallmayer J;Huguenard JR;Paşca SP
通讯作者：
Paşca SP