Whole-organ and whole-body 3D atlases enable cellome-wide profiling

Abstract

Recent advancements in tissue clearing and light-sheet fluorescence microscopy have enabled whole-organ/body-scale analysis at single-cell resolution. However, comprehensive bioinformatics resources like digitized whole-cellome maps, analogous to whole-genome sequencing, remain limited. Here, we present the CUBIC Organ/Body Atlas, a set of three-dimensional single-cell-resolution references for eleven adult mouse organs and a neonatal whole-mouse body. To generate this atlas, we optimized tissue clearing protocols and developed exMOVIE, an imaging system achieving sufficient working distance and axial resolution for organ-/body-wide three-dimensional imaging and subsequent cell nuclei detection. The atlas facilitates comparative analysis among multiple samples at single-cell resolution, allowing for applications in organ development studies, disease state analysis, and whole-body immune cell profiling with three-dimensional immunostaining. Thus, the CUBIC Organ/Body Atlas contributes to establishing a common cellomics workflow, advancing our systems-level understanding of organisms in physiological, developmental, and pathological processes.

Keywords: 3D imaging; CUBIC; atlas; cellome-wide profiling; cellomics; immune system; light-sheet fluorescence microscopy; tissue clearing; whole body; whole organ.