Brain Structural Organization Revealed by Unbiased Cell-Type Distribution Clustering

Cell type composition across brain regions is a crucial anatomical factor shaping both local and long-range brain circuits. In this study, we employed single-cell resolution imaging of the mouse brain, combined with automated computational analyses, to map the distribution of thirty cell types defined by unique gene marker expressions across the entire brain. Leveraging Cre recombinase mouse models for cell type labeling, we generated a comprehensive atlas of cell-type-specific distributions throughout the male and female brain. This analysis revealed that major anatomical brain areas can be characterized by distinct cell-type composition signatures. Furthermore, these distributions provide a powerful framework for identifying and refining the boundaries of different brain regions through unbiased clustering of whole-brain cell density data. This includes mapping of cortical areas and layers, hippocampal subregions, and thalamic and hypothalamic nuclei. Our findings suggest that cell type composition is intricately linked to the structural organization of the brain, with even subtle variations potentially contributing to distinct, brain region-specific brain functions.