1 State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontiers Center for Brain Science, Department of Neurology, Institute for Translational Brain Research, Zhongshan Hospital, Fudan University, Shanghai 200032, China

2 Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, CA 95064, USA

Abstract

Mouse cortical radial glial cells (RGCs) are primary neural stem cells that give rise to cortical oligodendrocytes, astrocytes, and olfactory bulb (OB) GABAergic interneurons in late embryogenesis. There are fundamental gaps in understanding how these diverse cell subtypes are generated. Here, by combining single-cell RNA-Seq with intersectional lineage analyses, we show that beginning at around E16.5, neocortical RGCs start to generate ASCL1⁺EGFR⁺ apical multipotent intermediate progenitors (MIPCs), which then differentiate into basal MIPCs that express ASCL1, EGFR, OLIG2, and MKI67. These basal MIPCs undergo several rounds of divisions to generate most of the cortical oligodendrocytes and astrocytes and a subpopulation of OB interneurons. Finally, single-cell ATAC-Seq supported our model for the genetic logic underlying the specification and differentiation of cortical glial cells and OB interneurons. Taken together, this work reveals the process of cortical radial glial cell lineage progression and the developmental origins of cortical astrocytes and oligodendrocytes.

Keywords

Radial glial cell; Intermediate progenitor cell; ASCL1; EGFR; OLIG2; Oligodendrocyte; Astrocyte; Olfactory bulb interneuron; Cerebral cortex

[SpringerLink][PMC Full Text]