Distinct progenitor behavior underlying neocortical gliogenesis related to tumorigenesis

Radial glial progenitors (RGPs) give rise to the vast majority of neurons and glia in the neocortex. Although RGP behavior and progressive generation of neocortical neurons have been delineated, the exact process of neocortical gliogenesis remains elusive. Here, we report the precise progenitor behavior and gliogenesis program at single-cell resolution in the mouse neocortex. Fractions of dorsal RGPs transition from neurogenesis to gliogenesis progressively, producing astrocytes, oligodendrocytes, or both in well-defined propensities of similar to 60%, 15%, and 25%, respectively, by fate-restricted intermediate precursor cells (IPCs). Although the total number of IPCs generated by individual RGPs appears stochastic, the output of individual IPCs exhibit clear patterns in number and subtype and form discrete local subclusters. Clonal loss of tumor suppressor Neurofibromatosis type 1 leads to excessive production of glia selectively, especially oligodendrocyte precursor cells. These results quantitatively delineate the cellular program of neocortical gliogenesis and suggest the cellular and lineage origin of primary brain tumor.

Automated summary

This study reveals the precise behavior of radial glial progenitors (RGPs) and the gliogenesis program in the mouse neocortex at single-cell resolution, showing the transition from neurogenesis to gliogenesis and the role of fate-restricted intermediate precursor cells (IPCs) in producing astrocytes and oligodendrocytes. It also highlights the impact of clonal loss of tumor suppressor Neurofibromatosis type 1 in excessive production of glia, especially oligodendrocyte precursor cells, quantitatively delineating the cellular program of neocortical gliogenesis and suggesting the cellular origin of primary brain tumors.