The human brain undergoes rapid development at mid-gestation from a pool of neural stem and progenitor cells (NSPCs) that give rise to the neurons, oligodendrocytes, and astrocytes of the mature brain. Functional study of these cell types has been hampered by a lack of precise purification methods. We describe a method for prospectively isolating ten distinct NSPC types from the developing human brain using cell-surface markers. CD24⁻THY1^−/lo cells were enriched for radial glia, which robustly engrafted and differentiated into all three neural lineages in the mouse brain. THY1^hi cells marked unipotent oligodendrocyte precursors committed to an oligodendroglial fate, and CD24⁺THY1^−/lo cells marked committed excitatory and inhibitory neuronal lineages. Notably, we identify and functionally characterize a transcriptomically distinct THY1^hiEGFR^hiPDGFRA⁻ bipotent glial progenitor cell (GPC), which is lineage-restricted to astrocytes and oligodendrocytes, but not to neurons. Our study provides a framework for the functional study of distinct cell types in human neurodevelopment.

人类大脑在妊娠中期经历了神经干细胞和祖细胞（NSPC）池的快速发育，这些细胞产生了成熟大脑的神经元、少突胶质细胞和星形胶质细胞。由于缺乏精确的纯化方法，这些细胞类型的功能研究受到阻碍。我们描述了一种使用细胞表面标记物从发育中的人脑中前瞻性分离十种不同 NSPC 类型的方法。 CD24 ^- THY1 ^-/lo细胞富含放射状胶质细胞，这些神经胶质细胞牢固地移植并分化为小鼠大脑中的所有三种神经谱系。 THY1 ^hi细胞标记了致力于少突胶质细胞命运的单能少突胶质细胞前体，CD24 ⁺ THY1 ^-/lo细胞标记了致力于兴奋性和抑制性神经元谱系。值得注意的是，我们鉴定并功能表征了转录组上不同的 THY1 ^hi EGFR ^hi PDGFRA ^-双能神经胶质祖细胞 (GPC)，其谱系仅限于星形胶质细胞和少突胶质细胞，但不限于神经元。我们的研究为人类神经发育中不同细胞类型的功能研究提供了一个框架。