Human cortical radial glial cells are primary neural stem cells that give rise to cortical glutaminergic projection pyramidal neurons, glial cells (oligodendrocytes and astrocytes) and olfactory bulb GABAergic interneurons. One of prominent features of the human cortex is enriched with glial cells, but there are major gaps in understanding how these glial cells are generated. Herein, by integrating analysis of published human cortical single-cell RNA-Seq datasets with our immunohistochemistical analyses, we show that around gestational week 18, EGFR-expressing human cortical truncated radial glial cells (tRGs) give rise to basal multipotent intermediate progenitors (bMIPCs) that express EGFR, ASCL1, OLIG2 and OLIG1. These bMIPCs undergo several rounds of mitosis and generate cortical oligodendrocytes, astrocytes and olfactory bulb interneurons. We also characterized molecular features of the cortical tRG. Integration of our findings suggests a general picture of the lineage progression of cortical radial glial cells, a fundamental process of the developing human cerebral cortex.

人皮质放射状神经胶质细胞是初级神经干细胞，可产生皮质谷氨酰胺能投射锥体神经元、神经胶质细胞（少突胶质细胞和星形胶质细胞）和嗅球 GABA 能中间神经元。人类皮层的突出特征之一是富含神经胶质细胞，但在理解这些神经胶质细胞是如何产生的方面存在重大差距。在此，通过将已发表的人类皮质单细胞 RNA-Seq 数据集的分析与我们的免疫组织化学分析相结合，我们表明在妊娠第 18 周左右，表达 EGFR 的人类皮质截短放射状胶质细胞 (tRGs) 会产生基底多能中间祖细胞 (bMIPCs) ) 表达 EGFR、ASCL1、OLIG2 和 OLIG1。这些 bMIPC 经历几轮有丝分裂并产生皮质少突胶质细胞、星形胶质细胞和嗅球中间神经元。我们还描述了皮质 tRG 的分子特征。我们的研究结果的整合表明了皮质放射状胶质细胞谱系进展的一般情况，这是人类大脑皮层发育的基本过程。