Multiple parallel cell lineages in the developing mammalian cerebral cortex. Multiple parallel cell lineages in the developing mammalian cerebral cortex

Cortical neurogenesis follows a simple lineage: apical Radial Glia Cells (RGC) generate basal progenitors, and these produce neurons. How this occurs in species with expanded germinal zones and a folded cortex, like human, remains unclear. We used single-cell RNA sequencing from individual cortical germinal zones in ferret, and barcoded lineage tracking, to determine the molecular diversity of progenitor cells and their lineages. We identified multiple RGC classes that initiate parallel lineages, converging onto a common class of newborn neuron. Parallel RGC classes and transcriptomic trajectories were repeated across germinal zones and conserved in ferret and human, but not mouse. Neurons followed parallel differentiation trajectories in gyrus and sulcus, with different expression of human cortical malformation genes. Progenitor cell lineage multiplicity is conserved in the folded mammalian cerebral cortex. This SuperSeries is composed of the SubSeries listed below. Overall design: Refer to individual Series Single-cell RNA sequencing (Borrell lab): https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE219254 Barcoded lineage tracking (Mayer lab): https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE233587