A Population-scale Single-cell Spatial Transcriptomic Atlas of the Human Cortex
Han, L.; Liu, Z.; Wang, L.; Liu, Y.; Wei, Y.; Ma, J.; He, Y.; Zuo, Y.; Fang, J.; Yang, H.; Zou, X.; Wu, Z.; Wang, M.; Liu, W.; Gao, L.; Liu, Y.; Song, X.; Zhang, Y. S.; Lei, J.; Li, H.; Li, L.; An, Y.; Jin, B.; Zhong, Y.; Chai, Q.; Tao, Q.; Tan, X.; Lin, Y.; Zhang, R.; Wang, S.; Chang, M.; Yang, B.; Chen, M.; Mi, L.; Zhuang, L.; Yuan, N.; Li, C.; Huang, T.; Li, X.; Liu, C.; Sun, Y.; Chen, L.; Liu, L.; Xu, X.; Li, C.; Guo, H.; Li, H.; Poo, M.; Gan, W.-B.; Yao, J.; Yuan, W.; Liu, S.; Shen, Z.; Mao, Y.; Wei, W.
Show abstract
The genetic and spatial determinants of cell type diversity in human cerebral cortices remain poorly defined. Here, we present a population-level single-cell spatial transcriptomic atlas of human cortices from 71 donors across the lifespan. We identified 906 layer-specific genes showing conserved and divergent laminar expression patterns between humans and other species. Spatial analysis revealed neuronal vulnerability and glial activation during aging, together with a decline in the proportion of superficial SST neurons and their interactions with other cells. Disease-associated genes exhibited high cell-type and layer-specific expression, implicating the pathogenic role of spatially specific gene expression. Spatial cis-eQTL analysis identified regulatory variants linked to genes related to diseases like Tourette syndrome. Cross-species comparison demonstrated glial expansion in the human cortex, accompanied by enhanced neuron-glia communication via the neuregulin signaling. Together, we provide a comprehensive single-cell atlas of the human cortex that is essential for understanding aging, evolution, and disease pathogenesis.
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