Margarette H. Clevenger, Denis Cipurko, Ashwini Patil, Bohan Li, Michihiro Takahama, Linghan Mei, Madison Plaster, Gabriella Richey, Tadafumi Kawamoto, Feng Bao, Nicolas Chevrier
The laboratory mouse is a key model system for biomedical research, yet body-wide measurement tools are lacking. Here, we generate spatiotranscriptomics profiles of whole-mouse sections that accurately capture histological regions. We spatially assign 379 cell types across whole-mouse section profiles by building a reference dataset of 59M single cells coupled with a scalable computational method for cell-type assignment. Moreover, we exploit these whole-mouse profiles to create a machine learning pipeline, LABEL, which enables pan-body annotation of tissues and cell types on histology images from H&E-stained sections. Lastly, we apply whole-mouse spatial profiling to map systemic inflammation in endotoxemia, which delineates organism-wide changes in gene expression programs across tissues and cell types. Together, our work paves the way for body-wide studies of the molecular and cellular processes that govern the organismal biology of the laboratory mouse across space, time, and conditions.