Molecular zonation of the human striatum across cell types and people

Growing functional, physiological, and molecular evidence suggest substantial heterogeneity of the human striatum's topography. To recognize spatial molecular variation across the striatum, we applied Slide-tags, a spatial transcriptomics platform that enables scalable spatial transcriptomics at single-nucleus resolution. Arrays spanning 7cm2 per donor captured cell type distributions from >500,000 cells across the anterior striatal compartments from 20 postmortem donors. Unsupervised clustering revealed that D1 and D2 medium spiny neurons were distributed in mosaic zones that ignored traditional neuroanatomical boundaries yet were shared across people; each zone combined discrete marker genes with superimposed larger-scale expression gradients. Intriguingly, astrocytes also displayed zonation, whereas other glial types did not. Spatial imputation of 3 million additional snRNA-seq profiles from 150 donors defined age and genetic variation across zone-specific gene expression programs. Our molecularly defined striatal cytoarchitectural map provides a scaffold for investigations of striatal circuit assembly and selective vulnerability to brain disease.

Data citation

No data citation listed

Funding agency

NIMH

Grant numbers

UM1MH130966

Access

open

License

CC BY 4.0