单细胞RNA测序揭示了人类前额叶皮层的发育图谱

Mammalian prefrontal cortex contains billions of cells, some of which are known as neurons to play critical roles in memory, cognitive ability, decision making, social behavior etc. through participating into complex neural circuits. Although neural circuits build up in the late stage of human embryo development and even after birth, the diverse and functional cells start to generate and migrate to the appropriate location play essential roles as basis for developing future circuits. However, it remains challenging to identify cell types of developing human PFC and distinguish their developmental features. Here, to address these challenges, single cells from human embryos PFC were carried out for RNA-seq. Detailed analysis of neural progenitor cells (NPCs) illustrated a developmental feature of intermediate progenitor (IP) cells and revealed new marker genes of IP cells. We also mapped the neurogenesis timeline of PFC excitatory neurons and intrinsic singles regulating neuron maturation and circuit formation. Our screening and characterization approach provides a blueprint of human PFC development in early and mid embryonic stages, with which to systematically discover the cellular basis and molecular regulation of PFC function in humans.

哺乳动物前额叶皮层（prefrontal cortex, PFC）包含数十亿细胞，其中神经元（neurons）通过参与复杂神经环路，在记忆、认知能力、决策、社会行为等诸多方面发挥关键作用。尽管神经环路在人类胚胎发育后期乃至出生后才逐步构建，但具有多样性与功能特性的细胞会在早期阶段开始产生并迁移至适宜位置，为后续神经环路的发育奠定核心基础。然而，鉴定发育中的人类前额叶皮层的细胞类型并区分其发育特征仍颇具挑战。为此，本研究针对人类胚胎前额叶皮层的单细胞开展了RNA测序（RNA-seq）实验。对神经祖细胞（neural progenitor cells, NPCs）的详细分析揭示了中间祖细胞（intermediate progenitor cells, IP cells）的发育特征，并鉴定出IP细胞的全新标记基因。本研究还绘制了前额叶皮层兴奋性神经元的神经发生时间线，并解析了调控神经元成熟与环路形成的内在信号。我们的筛选与表征策略为人类胚胎早中期的前额叶皮层发育提供了一套研究蓝图，借此可系统性解析人类前额叶皮层功能的细胞基础与分子调控机制。

搜集汇总

背景与挑战

背景概述

该数据集通过单细胞RNA测序技术，对人类胚胎前额叶皮层的发育过程进行了深入研究，揭示了神经祖细胞的发育特征和兴奋性神经元的神经发生时间线。数据集包含39个样本，覆盖孕周23周和26周等胚胎阶段，数据量达884.74 GB，为理解人类前额叶皮层的细胞基础和分子调控提供了重要资源。