Close Jennie L, Yao Zizhen, Levi Boaz P, Miller Jeremy A, Bakken Trygve E, Menon Vilas, Ting Jonathan T, Wall Abigail, Krostag Anne-Rachel, Thomsen Elliot R, Nelson Angel M, Mich John K, Hodge Rebecca D, Shehata Soraya I, Glass Ian A, Bort Susan, Shapovalova Nadiya V, Ngo N Kiet, Grimley Joshua S, Phillips John W, Thompson Carol L, Ramanathan Sharad, Lein Ed
Allen Institute for Brain Science, Seattle, WA 98109, USA.
Allen Institute for Brain Science, Seattle, WA 98109, USA.
Neuron. 2017 Mar 8;93(5):1035-1048.e5. doi: 10.1016/j.neuron.2017.02.014.
GABAergic interneurons are essential for neural circuit function, and their loss or dysfunction is implicated in human neuropsychiatric disease. In vitro methods for interneuron generation hold promise for studying human cellular and functional properties and, ultimately, for therapeutic cell replacement. Here we describe a protocol for generating cortical interneurons from hESCs and analyze the properties and maturation time course of cell types using single-cell RNA-seq. We find that the cell types produced mimic in vivo temporal patterns of neuron and glial production, with immature progenitors and neurons observed early and mature cortical neurons and glial cell types produced late. By comparing the transcriptomes of immature interneurons to those of more mature neurons, we identified genes important for human interneuron differentiation. Many of these genes were previously implicated in neurodevelopmental and neuropsychiatric disorders.
γ-氨基丁酸能中间神经元对神经回路功能至关重要，其丧失或功能障碍与人类神经精神疾病有关。体外生成中间神经元的方法有望用于研究人类细胞和功能特性，并最终用于治疗性细胞替代。在此，我们描述了一种从人胚胎干细胞生成皮质中间神经元的方案，并使用单细胞RNA测序分析细胞类型的特性和成熟时间进程。我们发现所产生的细胞类型模拟了体内神经元和胶质细胞产生的时间模式，早期观察到未成熟祖细胞和神经元，后期产生成熟皮质神经元和胶质细胞类型。通过比较未成熟中间神经元与更成熟神经元的转录组，我们确定了对人类中间神经元分化重要的基因。其中许多基因先前与神经发育和神经精神疾病有关。
