This research study presents a systematic single-cell transcriptomic atlas designed to understand how various morphogens direct the regional patterning of the human central nervous system in vitro. By analyzing over 100,000 cells across multiple human pluripotent stem cell lines, the authors examined how the timing and concentration of signaling molecules like SHH, FGF8, and RA influence the emergence of specific brain identities. The data reveal that specific gene regulatory networks, or regulons, respond uniquely to these chemical cues, allowing for the targeted activation of developmental programs for the forebrain, midbrain, and spinal cord. Additionally, the researchers compared traditional 3D organoids with a microfluidic MiSTR model, highlighting how physical tissue architecture and morphogen gradients impact cellular diversity. The findings provide a comprehensive resource for optimizing organoid protocols and offer new insights into the complex interactions that govern early human brain development. This work ultimately aims to improve the reproducibility and accuracy of stem cell-derived models used in neurobiological research.

References:

• Sanchís-Calleja F, Azbukina N, Jain A, et al. Systematic scRNA-seq screens profile neural organoid response to morphogens[J]. Nature Methods, 2025: 1-14.