A single-cell RNA-seq survey of the developmental landscape of the human prefrontal cortex
A single-cell RNA-seq survey of the developmental landscape of the human prefrontal cortex
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对人类前额皮质发育景观的单细胞 RNA 测序调查
DOI：
10.1038/nature25980
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发表时间：
2018-03-22
期刊：
影响因子：
64.8
通讯作者：
Wang, Xiaoqun
中科院分区：
文献类型：
--
作者：
Zhong, Suijuan;Zhang, Shu;Wang, Xiaoqun
哺乳动物的前额叶皮质由一组包含数十亿个细胞的高度专业化的脑区组成，是最高级认知功能的中心，如记忆、认知能力、决策和社会行为。虽然神经回路是在人类胚胎发育的后期形成的，甚至在出生后也会形成，但不同类别的功能细胞会在发育早期产生并迁移到适当的位置。前额叶皮质功能障碍导致认知障碍和大多数神经发育障碍；因此，有必要详细了解前额叶皮质的发育。然而，对发育中的人类前额叶皮质的细胞类型及其发育特征的区分仍然是困难的。在这里，我们使用RNA测序技术分析了8到26周发育中的人类前额叶皮质中的2300多个单细胞。我们识别了六个主要类别的35种细胞亚型，并追踪了这些细胞的发育轨迹。对神经前体细胞的详细分析突出了中间前体细胞的新标记基因和独特的发育特征。我们还绘制了前额叶皮质兴奋性神经元神经发生的时间表，并检测了早期发育的前额叶皮质中神经元间前体细胞的存在。此外，我们通过单细胞转录数据分析揭示了调节神经元生成和电路形成的内在发育相关信号。我们的筛选和鉴定方法为了解人类妊娠早期和中期前额叶皮质的发育提供了蓝图，以便系统地剖析人类前额叶皮质功能的细胞基础和分子调控。
The mammalian prefrontal cortex comprises a set of highly specialized brain areas containing billions of cells and serves as the centre of the highest-order cognitive functions, such as memory, cognitive ability, decision-making and social behaviour,. Although neural circuits are formed in the late stages of human embryonic development and even after birth, diverse classes of functional cells are generated and migrate to the appropriate locations earlier in development. Dysfunction of the prefrontal cortex contributes to cognitive deficits and the majority of neurodevelopmental disorders; there is therefore a need for detailed knowledge of the development of the prefrontal cortex. However, it is still difficult to identify cell types in the developing human prefrontal cortex and to distinguish their developmental features. Here we analyse more than 2,300 single cells in the developing human prefrontal cortex from gestational weeks 8 to 26 using RNA sequencing. We identify 35 subtypes of cells in six main classes and trace the developmental trajectories of these cells. Detailed analysis of neural progenitor cells highlights new marker genes and unique developmental features of intermediate progenitor cells. We also map the timeline of neurogenesis of excitatory neurons in the prefrontal cortex and detect the presence of interneuron progenitors in early developing prefrontal cortex. Moreover, we reveal the intrinsic development-dependent signals that regulate neuron generation and circuit formation using single-cell transcriptomic data analysis. Our screening and characterization approach provides a blueprint for understanding the development of the human prefrontal cortex in the early and mid-gestational stages in order to systematically dissect the cellular basis and molecular regulation of prefrontal cortex function in humans.