利用脑类器官研究神经发育与疾病。
The use of brain organoids to investigate neural development and disease.
作者信息
Di Lullo Elizabeth, Kriegstein Arnold R
机构信息
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, California 94143, USA.
Department of Neurology, University of California, San Francisco, California 94158, USA.
出版信息
Nat Rev Neurosci. 2017 Oct;18(10):573-584. doi: 10.1038/nrn.2017.107. Epub 2017 Sep 7.
Abstract
Understanding the development and dysfunction of the human brain is a major goal of neurobiology. Much of our current understanding of human brain development has been derived from the examination of post-mortem and pathological specimens, bolstered by observations of developing non-human primates and experimental studies focused largely on mouse models. However, these tissue specimens and model systems cannot fully capture the unique and dynamic features of human brain development. Recent advances in stem cell technologies that enable the generation of human brain organoids from pluripotent stem cells (PSCs) promise to profoundly change our understanding of the development of the human brain and enable a detailed study of the pathogenesis of inherited and acquired brain diseases.
摘要
了解人类大脑的发育和功能障碍是神经生物学的一个主要目标。我们目前对人类大脑发育的许多理解都来自对死后和病理标本的检查，同时，对发育中的非人类灵长类动物的观察以及主要集中在小鼠模型上的实验研究也起到了支持作用。然而，这些组织标本和模型系统无法完全捕捉人类大脑发育的独特和动态特征。干细胞技术的最新进展使得从多能干细胞（PSC）生成人类脑类器官成为可能，这有望深刻改变我们对人类大脑发育的理解，并能够对遗传性和获得性脑部疾病的发病机制进行详细研究。
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本文引用的文献
1
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Nat Methods. 2017 Jul;14(7):743-751. doi: 10.1038/nmeth.4304. Epub 2017 May 10.
2
Migrating Interneurons Secrete Fractalkine to Promote Oligodendrocyte Formation in the Developing Mammalian Brain.迁移中间神经元分泌 fractalkine 以促进哺乳动物大脑发育中的少突胶质细胞形成。
Neuron. 2017 May 3;94(3):500-516.e9. doi: 10.1016/j.neuron.2017.04.018.
3
Assembly of functionally integrated human forebrain spheroids.功能性整合的人类前脑类器官的组装。
Nature. 2017 May 4;545(7652):54-59. doi: 10.1038/nature22330. Epub 2017 Apr 26.
4
Cell diversity and network dynamics in photosensitive human brain organoids.光敏性人脑类器官中的细胞多样性与网络动力学
Nature. 2017 May 4;545(7652):48-53. doi: 10.1038/nature22047. Epub 2017 Apr 26.
5
Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells.人脑神经上皮干细胞来源的中脑组织类器官的建立。
Stem Cell Reports. 2017 May 9;8(5):1144-1154. doi: 10.1016/j.stemcr.2017.03.010. Epub 2017 Apr 13.
6
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7
Self-organized developmental patterning and differentiation in cerebral organoids.大脑类器官中的自组织发育模式形成与分化
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9
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