Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex

TLDR

Systematic analyses of spatiotemporal gene expression during organogenesis are difficult because diverse cell types at varying maturation stages coexist in emerging tissues. We mapped discrete cell types and temporally and spatially restricted radial glia maturation trajectories, revealing early neurogenic transcription factor expression, enriched mTOR signaling in outer radial glia, and modest radial glia transcriptional differences that drive robust neuronal typological distinctions, supporting a mixed model of topographical, typological, and temporal hierarchies in human telencephalon development.

Abstract

Systematic analyses of spatiotemporal gene expression trajectories during organogenesis have been challenging because diverse cell types at different stages of maturation and differentiation coexist in the emerging tissues. We identified discrete cell types as well as temporally and spatially restricted trajectories of radial glia maturation and neurogenesis in developing human telencephalon. These lineage-specific trajectories reveal the expression of neurogenic transcription factors in early radial glia and enriched activation of mammalian target of rapamycin signaling in outer radial glia. Across cortical areas, modest transcriptional differences among radial glia cascade into robust typological distinctions among maturing neurons. Together, our results support a mixed model of topographical, typological, and temporal hierarchies governing cell-type diversity in the developing human telencephalon, including distinct excitatory lineages emerging in rostral and caudal cerebral cortex.