Generation of cerebral corticalGABAergicinterneurons from pluripotent stem cells
Generation of cerebral corticalGABAergicinterneurons from pluripotent stem cells
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DOI：
10.1002/stem.3252
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发表时间：
2020-09-02
期刊：
影响因子：
5.2
通讯作者：
Anderson，Stewart A.
中科院分区：
文献类型：
--
作者：
Fitzgerald，Megan;Sotuyo，Nathaniel;Anderson，Stewart A.
大脑皮层的功能是由内在和外在神经元活动、神经胶质细胞活动和体液因素的影响的复杂相互作用实现的。内在神经元的影响由两个主要的亚类介导：兴奋性谷氨酸能神经元和抑制性GABA能神经元，兴奋性谷氨酸能神经元通常具有延伸超出神经元局部的轴突投射，抑制性GABA能神经元通常局部投射。这些中间神经元可以根据形态学、神经化学、电生理学、轴突靶向和回路影响特征进行分组。皮质中间神经元（CIns）也可以根据其在皮质下端脑内的起源进行分组。中间神经元亚型，其中一打或更多被认为存在，其特征在于这些亚组特征的组合。由于它们与神经精神障碍的原因和治疗的充分记录的相关性，以及它们在移植后广泛迁移的显著能力，人们对从人多能干细胞产生皮质GABA能中间神经元产生了极大的兴趣。在这篇简要的综述中，我们讨论了最近的进展，了解如何在体内产生的interneuron亚型，以及如何将这一进展应用于在体外产生的啮齿动物和人类CIN。此外，我们将讨论在移植研究中严格指定中间神经元亚群或亚型的方法，以及该领域的挑战，包括人类中间神经元的长期成熟。意义声明以神经精神症状为特征的多种前脑“中间神经元病”的鉴定，以及胚胎来源的中间神经元在以前脑去抑制为特征的疾病啮齿动物模型中移植的疗效，从多能干细胞衍生大脑皮层GABA能中间神经元引起了极大的兴趣。本文综述了干细胞衍生的皮质中间神经元在前脑疾病的研究和治疗中的应用进展和面临的挑战。
The cerebral cortex functions by the complex interactions of intrinsic and extrinsic neuronal activities, glial actions, and the effects of humoral factors. The intrinsic neuronal influences are mediated by two major subclasses: excitatory glutamatergic neurons that generally have axonal projections extending beyond the neuron's locality and inhibitory GABAergic neurons that generally project locally. These interneurons can be grouped based on morphological, neurochemical, electrophysiological, axonal targeting, and circuit influence characteristics. Cortical interneurons (CIns) can also be grouped based on their origins within the subcortical telencephalon. Interneuron subtypes, of which a dozen or more are thought to exist, are characterized by combinations of these subgrouping features. Due to their well-documented relevance to the causes of and treatments for neuropsychiatric disorders, and to their remarkable capacity to migrate extensively following transplantation, there has been tremendous interest in generating cortical GABAergic interneurons from human pluripotent stem cells. In this concise review, we discuss recent progress in understanding how interneuron subtypes are generated in vivo, and how that progress is being applied to the generation of rodent and human CIns in vitro. In addition, we will discuss approaches for the rigorous designation of interneuron subgroups or subtypes in transplantation studies, and challenges to this field, including the protracted maturation of human interneurons.Significance statementThe identification of multiple forebrain “interneuronopathies” featuring neuropsychiatric symptoms, as well as the efficacy of transplants of embryo-derived interneurons in rodent models of disorders featuring forebrain disinhibition, has engendered tremendous interest in deriving cerebral cortical GABAergic interneurons from pluripotent stem cells. This review considers progress in this derivation and the remaining challenges to the use of stem cell-derived cortical interneurons in the study and treatment of forebrain disease.