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单细胞甲基组在哺乳动物皮层中识别神经元亚型和调节元素

Chongyuan Luo^1,2, Christopher L Keown³, Laurie Kurihara⁴

¹Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

Science (New York, N.Y.)

|August 12, 2017

概括

研究人员在6000多个单个脑细胞中绘制了DNA甲基化图, 识别了小鼠和人类中不同的神经元亚型. 这种表观基因图谱揭示了对脑细胞多样性至关重要的细胞特异性调节元素.

科学领域:

神经科学
表观遗传学
基因组学

背景情况:

哺乳动物的大脑表现出惊人的神经元多样性,但对单细胞的全面描述仍然具有挑战性.
DNA甲基化作为稳定的表观遗传标记,对细胞类型的识别和调控元素的定义至关重要.

研究的目的:

开发和应用单核表观基因分析来识别和描述多样化的神经元群体.
研究细胞类型特定的DNA甲基化模式及其在神经元多样性中的作用.

主要方法:

从小鼠和人类的额叶皮层生成超过6000个单核甲基组.
在神经元亚型中分析CG和非CG甲基化分布.
不同甲基化调节元件的识别.

主要成果:

基于甲基化特征发现了16个小鼠和21个人类神经元子群.
特定的第六层激发性神经元亚型和独特的人类帕瓦胺表达性抑制性神经元亚型的鉴定.
与激发性神经元相比,抑制性神经元的调节元件在跨物种中保持较大.

结论:

单核甲基组提供了大脑细胞类型的扩展图谱.
表观遗传学特征揭示了驱动大脑细胞多样性的调节因素.
这种方法提高了我们对神经元异质性和进化的理解.

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