Systematic cell-type resolved transcriptomes of 8 tissues in 8 lab and wild-derived mouse strains capture global and local expression variation.

Mapping the impact of genomic variation on gene expression provides insight into the molecular basis of complex phenotypic traits and disease predisposition. Mouse models offer a controlled framework to capture genomic diversity across tissues. As part of the IGVF consortium, we profiled the transcriptomes of eight tissues from each founder strain of the Collaborative Cross using single-nucleus RNA sequencing. The resulting "8-cube" dataset contains 5.2 million nuclei across 106 cell types and cell states. Transcriptome variation correlated with genetic divergence, highest in the wild-derived strains. Heart and brain were relatively similar, whereas gonads, adrenal gland, skeletal muscle, kidney, and liver showed greater divergence. Variation often concentrated in specific cell types and states, especially those linked to immune and metabolic traits. The founder 8-cube dataset provides rich transcriptome signatures to help explain strain-specific traits and disease states and serves as a foundation for deeper analysis of these tissues across diverse mouse genotypes.