Crompton Lucy A, Cordero-Llana Oscar, Caldwell Maeve A
School of Biochemistry, Medical Sciences Bld, University of Bristol, Bristol, BS8 1TD, UK.
Bristol Medical School, Medical Sciences Bld, University of Bristol, Bristol, BS8 1TD, UK.
Brain Pathol. 2017 Jul;27(4):530-544. doi: 10.1111/bpa.12522.
Neuroscience and Neurobiology have historically been neuron biased, yet up to 40% of the cells in the brain are astrocytes. These cells are heterogeneous and regionally diverse but universally essential for brain homeostasis. Astrocytes regulate synaptic transmission as part of the tripartite synapse, provide metabolic and neurotrophic support, recycle neurotransmitters, modulate blood flow and brain blood barrier permeability and are implicated in the mechanisms of neurodegeneration. Using pluripotent stem cells (PSC), it is now possible to study regionalised human astrocytes in a dish and to model their contribution to neurodevelopmental and neurodegenerative disorders. The evidence challenging the traditional neuron-centric view of degeneration within the CNS is reviewed here, with focus on recent findings and disease phenotypes from human PSC-derived astrocytes. In addition we compare current protocols for the generation of regionalised astrocytes and how these can be further refined by our growing knowledge of neurodevelopment. We conclude by proposing a functional and phenotypical characterisation of PSC-derived astrocytic cultures that is critical for reproducible and robust disease modelling.
神经科学和神经生物学在历史上一直以神经元为研究重点，然而大脑中高达40%的细胞是星形胶质细胞。这些细胞具有异质性且在区域上存在差异，但对大脑的稳态至关重要。星形胶质细胞作为三方突触的一部分调节突触传递，提供代谢和神经营养支持，回收神经递质，调节血流和脑血屏障通透性，并与神经退行性变机制有关。利用多能干细胞（PSC），现在可以在培养皿中研究区域化的人类星形胶质细胞，并模拟它们对神经发育和神经退行性疾病的作用。本文综述了挑战中枢神经系统内传统以神经元为中心的退化观点的证据，重点关注来自人类PSC衍生星形胶质细胞的最新发现和疾病表型。此外，我们比较了目前生成区域化星形胶质细胞的方案，以及随着我们对神经发育的认识不断增加，这些方案如何能够进一步完善。我们通过提出对PSC衍生星形胶质细胞培养物的功能和表型特征描述来得出结论，这对于可重复和稳健的疾病建模至关重要。
