Clonal lineage tracing and transcriptomics of cortical progenitor populations reveal maintenance of differentiation potential.

Postnatal neocortical development is a complex period wherein radial glial progenitors complete excitatory neurogenesis and transition to the production of glia. Here, we take advantage of a multi-layered lineage tracing tool pbacBarcode, to examine the contributions of individual cortical RGPs to the postnatal cortex. We reveal that some individual cortical RGPs are multipotent and give rise to olfactory bulb interneurons, astrocytes, and oligodendrocytes in a ~2:1:1 ratio. We provide evidence that differentiation potential into terminal cell types is maintained as late as P4, suggesting a population decline model, as opposed to cell fate restriction, underlies cortical progression . Moreover, a pool of proliferative intermediary cells which may represent a multipotent postnatal intermediate progenitor cell population may contribute to the production of the three major cell types. Lastly, we examine RGP postnatal contribution to oligodendrocytes and show that oligodendrocyte progenitor founder cell production by cortical RGPs is largely complete by P3. Single-cell RNA-sequencing of mouse neocortex electroporated at E14.5 and collected at P4. Curio Seeker spatial transcriptomics of wild-type P4 and P22 mouse forebrain.