Conservation and divergence of cortical cell organization in human and mouse revealed by MERFISH

The human cerebral cortex has tremendous cellular diversity. How different cell types are organized in the human cortex and how cellular organization varies across species remain unclear. Here, we performed spatially resolved single-cell profiling of 4,000 genes using multiplexed error-robust FISH (MERFISH), identified >100 transcriptionally distinct cell populations, and generated a molecularly defined and spatially resolved cell atlas of the human middle and superior temporal gyrus. We further explored cell-cell interactions arising from soma contact or proximity in a cell-type-specific manner. Comparison with the mouse cortex showed conservation in the laminar organization of cells and differences in somatic interactions across species. Notably, our data revealed human-specific cell-cell proximity patterns and showed a markedly increased enrichment for interactions between neurons and non-neuronal cells in the human cortex.