Spatial single-cell mapping of transcriptional differences across genetic backgrounds in mouse brains.

ATLAS spatially maps atlas-scale transcriptomes in mouse brains, detecting more than 40 significant cell-type distribution differences and 16 regional composition changes across B6 versus BTBR and male versus female comparisons.

• Why it matters: Genetic background can shift organ structure and function, but comparative statistics need spatial, single-cell, atlas-scale data with replicates across genotypes and sexes.
• What they did: The method learns aggregate transcriptional signatures from single-cell RNA-seq, encodes them in situ with tens of thousands of oligonucleotide probes, and decodes cell types and imputed transcriptomes; it was validated against MERFISH and four other technologies.
• The result: Profiling 40 million cells across 400+ coronal sections from C57BL/6J and BTBR T + tf/J mice reveals more than 40 significant differences in cell-type distributions and 16 regional composition changes, enabling systematic structure–function comparisons in disease models.

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