Transcriptional dysregulation in postnatal glutamatergic progenitor contributes to closure of the cortical neurogenic period

Glutamatergic progenitors persist in the forebrain long after the period of corticogenesis. We performed fate-mapping of pre- and postnatal glutamatergic progenitors to investigate their lineage relationship and neuronal output. Our results show that postnatal glutamatergic progenitors do not accumulate during embryonic development, but are produced by embryonic radial glial cells that persist after birth in the dorsal subventricular zone. Whereas most undergo delayed cell death, some of these progenitors give rise to cortical neurons that express markers of late born neurons, but ectopically migrate to deep cortical layers where they survive for at least several weeks. Single cell RNA-sequencing reveal a downregulation of transcriptional programs, specifically those involved in metabolism, differentiation and migration, which parallels the gradual decline in cortical neurogenesis observed in vivo. Rescuing experiments show that postnatal progenitors remain permissive to genetic and pharmacological manipulation, suggesting that they could be recruited for regenerative purposes. Our study is the first to provide an in depth characterization of postnatal glutamatergic progenitors and identifies novel potential therapeutic targets for promoting brain repair