PT - JOURNAL ARTICLE AU - Chih-Wei Hsu AU - Juan Cerda III AU - Jason M. Kirk AU - Williamson D. Turner AU - Tara L. Rasmussen AU - Carlos P. Flores Suarez AU - Mary E. Dickinson AU - Joshua D. Wythe TI - EZ Clear for simple, rapid, and robust mouse whole organ clearing AID - 10.1101/2022.01.12.476113 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.01.12.476113 4099 - http://biorxiv.org/content/early/2022/01/13/2022.01.12.476113.short 4100 - http://biorxiv.org/content/early/2022/01/13/2022.01.12.476113.full AB - Tissue clearing for whole organ cell profiling has revolutionized biology and imaging for exploration of organs in three-dimensional space without compromising tissue architecture. But complicated, laborious procedures, or expensive equipment, as well as the use of hazardous, organic solvents prevents the widespread adoption of these methods. Here we report a simple and rapid tissue clearing method, EZ Clear, that can clear whole adult mouse organs in 48 hours in just three simple steps. Samples stay at room temperature and remain hydrated throughout the clearing process, preserving endogenous and synthetic fluorescence, without altering sample size. After wholemount clearing and imaging, EZ Cleared samples can be further processed for downstream embedding and cryosectioning followed by standard histology or immunostaining, without loss of endogenous or synthetic fluorescence signal. Overall, the simplicity, speed, and flexibility of EZ Clear make it easy to adopt and apply to diverse approaches in biomedical research.Competing Interest StatementThe authors have declared no competing interest.