Developmental Origins of Human Cortical Oligodendrocytes and Astrocytes

 Lin Yang1 • Zhenmeiyu Li1 • Guoping Liu1 • Xiaosu Li1 • Zhengang Yang1
1 State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Institute for Translational Brain Research, and Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
 
Abstract
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 singlecell RNA-Seq datasets with our immunohistochemistical analyses, we show that around gestational week 18, EGFRexpressing 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.
 
Keywords
Radial glial;cell Intermediate;progenitor cell;EGFR; HOPX; Oligodendrocyte; Astrocyte; Olfactory bulb interneuron; Cerebral cortex; Human