DECODING CELLULAR AND TEMPORAL VARIABILITY IN HUMAN CORTICAL DEVELOPMENT. INTEGRATING SINGLE-CELL TRANSCRIPTOMICS ACROSS DEVELOPMENTAL STAGES AND EXPERIMENTAL MODELS.

The human cortex is composed of heterogeneous neurons and glia that interact to facilitate complex brain functions. However, studying their development over decades has been technically challenging due to limitations in data access and representation. Recent advances in single-cell profiling have provided a wealth of data on fetal and adult human cortex cells, but extracting insights from this information remains a significant hurdle. To address this challenge, we present NeuRoDev, an innovative analytical and data resource that leverages existing data to resolve temporal and cellular variability across the entire process of human cortex development. From 5 weeks post-conceptional to 65 years of age, NeuRoDev provides a highly curated data platform with simple analytical tools to facilitate the study of brain cell physiology. NeuRoDev achieves this by introducing an integrative network-based approach that connects reproducible transcriptional patterns across single-cell transcriptomes. This framework enables the contextualization of gene function and iPSC-derived experimental models within human neurodevelopment, providing new insights into the dynamics of cellular processes and the basis of brain disorders. We use NeuRoDev to investigate cell physiological processes, neuronal and glial cell maturation, and collective behavior in brain disorders. All analytical tools and data resources are freely available through the R packages NeuRoDev and NeuRoDevDB.