Fig. 1.

Resolving the tree of neural progenitor cell differentiation during human corticogenesis. (A) Schematic of analyses implemented in this paper: single-cell trajectory reconstruction of basal progenitor generation, for the inference and recovery of gene regulatory networks and expression programs, illuminated by paleogenomic analysis. (B,C) Identifying the main axis of variation using principal component analysis (PCA) is a powerful strategy to characterize the heterogeneity and transcriptional dynamics of progenitor cells [as shown for example in a comprehensive study in mice (Mukhtar et al., 2022)]. Here, we performed PCA on a single-cell dataset of human neural progenitors, which allowed the discrimination of radial glia and intermediate progenitor cell subtypes (coarse clustering, B). Top gene loadings with known markers of neural progenitor subtypes are shown in C. (D,E) Inferred tree of principal points and associated dendrogram capturing the hierarchy of neural cell lineage relationships as inferred from single-cell data. (F) Expression trajectory along pseudotime of three marker genes for ventricular radial, outer radial glia and intermediate progenitor cell clusters. (G) Heatmap with representative genes, the trajectories of which significantly change as pseudotime progresses.