Spatial transcriptomics reveal developmental dynamics of the human cerebral cortex and striatum

The human fetal brain undergoes morphological changes that contribute to the development of regional functionalities. However, the features of structural development, the underlying molecular and cellular signatures in the fetal brain, remain unclear. With spatial transcriptomics and single-nucleus RNA sequencing (snRNA-seq), we identified 25 forebrain regions and characterized the dynamic changes in the cortex and striatum during the late first and early second trimesters. In particular, we discovered that the temporal lobe enriched NPY-expressing L2/3 excitatory (EX) neurons potentially interacted with L4 EX neurons during cortical expansion and arealization. Additionally, the gyrus and sulcus were developmentally asynchronous, in which HOPX and SPARC genes were potentially involved. Further investigation on the striatum showed specific genes and cell types that were enriched in patch and matrix compartments, and SST-positive interneurons potentially involved in the development of these structures. Together, our results give insights into the understanding of early fetal brain development.