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Reviewer #1 (Public Review): Temporal transcriptomic dynamics in developing macaque neocortex
Résumé : Despite intense research on mice, the transcriptional regulation of neocortical neurogenesis remains limited in humans and non-human primates.Cortical development in rhesus macaque is known to recapitulate multiple facets of cortical development in humans, including the complex composition of neural stem cells and the thicker supragranular layer.To characterize temporal shifts in transcriptomic programming responsible for differentiation from stem cells to neurons, we sampled parietal lobes of rhesus macaque at E40, E50, E70, E80, and E90, spanning the full period of prenatal neurogenesis.Single-cell RNA sequencing produced a transcriptomic atlas of developing parietal lobe in rhesus macaque neocortex.Identification of distinct cell types and neural stem cells emerging in different developmental stages revealed a terminally bifurcating trajectory from stem cells to neurons.Notably, deep-layer neurons appear in the early stages of neurogenesis, while upper-layer neurons appear later.While these different lineages show overlap in their differentiation program, cell fates are determined post-mitotically.Trajectories analysis from ventricular radial glia (vRGs) to outer radial glia (oRGs) revealed dynamic gene expression profiles and identified differential activation of BMP, FGF, and WNT signaling pathways between vRGs and oRGs.These results provide a comprehensive overview of the temporal patterns of gene expression leading to different fates of radial glial progenitors during neocortex layer formation. eLife assessmentThis study presents a useful resource for the gene expression profiles of different cell types in the parietal lobe of the cerebral cortex of prenatal macaques.The evidence supporting the claims of the authors is solid, and revision has clarified some of the cell isolation and cell classification issues flagged by reviewers.This dataset will be of interest to developmental neurobiologists and could potentially be used for future comparative studies on early brain development.