UCSF

The human cortex is comprised of diverse cell types that emerge from an initially uniform neuroepithelium that gives rise to radial glia, the canonical neural stem cells of the cortex. To characterize the earliest stages of human brain development, I performed single-cell RNA-sequencing across regions of the developing human brain, including the telencephalon, diencephalon, midbrain, hindbrain, and cerebellum. I identify nine progenitor populations in or near the telencephalon, suggesting more heterogeneity than previously described, including a highly prevalent mesenchymal-like population that disappears once neurogenesis begins. Comparison of human and mouse progenitor populations at corresponding stages identifies two progenitor clusters that are enriched in the early stages of human cortical development. I also find that organoid systems display low fidelity to neuroepithelial and early radial glia cell types, but fidelity improves as neurogenesis progresses. In this thesis, I provide a comprehensive molecular and spatial atlas of early stages of human brain and cortical development.