Heterogeneity of glial progenitor cells during the neurogenesis-to-gliogenesis switch in the developing human cerebral cortex.

The heterogeneity and molecular characteristics of progenitor cells, especially glial progenitors, in the developing human cerebral cortex remain elusive. Here, we find that EGFR expression begins to sharply increase after gestational week (GW) 20, which corresponds to the beginning stages of human gliogenesis. In addition, EGFR+ cells are mainly distributed in the germinal zone and frequently colocalize with the stemness marker SOX2 during this period. Then, by performing single-cell RNA sequencing on these EGFR+ cells, we successfully enriched and characterized various glial- and neuronal-lineage progenitor cells and validated their phenotypes in fixed slices. Notably, we identified two subgroups with molecular characteristics similar to those of astrocytes, and the immunostaining results show that these cells are mainly distributed in the outer subventricular zone and might originate from the outer radial glial cells. In short, the EGFR-sorting strategy and molecular signatures in the diverse lineages provide insights into human glial development.