Molecular lineage and spatial distribution of subplate neurons in the human fetal cerebral cortex.

Subplate neurons (SPNs) are among the firstborn neurons in the human fetal cerebral cortex, and play a critical role in establishing intra- and extracortical connections. In this study, we created spatial landscapes and molecular lineages of SPNs by performing spatial transcriptomics, and revealed precise position information of various cortical cell types including subplate neurons and their high diversity in the human fetal cortex. Through the spatial distribution of subplate neurons, we identified the molecular signatures of subplate neurons that are closer to early-born neurons than late-born neurons. We also analyzed human-specific genes and extracellular matrix genes enriched in subplate neurons, highlighting the potential contributions of subplate neurons to cortical neurogenesis and early structural folding. Overall design: Cerebral cortex tissue sections from fetal (gestational week 12 and 13) were subject to spatial transcriptomics analysis.