Hustin, L. S.; Conrad, C.; Liu, C.; Fuentealba, J.; Menegatti, S.; Shneer, S.; Battistella, A.; Tabarin, F.; Weber, T. S.; Amigorena, S.; Duffy, K. R.; Perie, L.

Cell division drives multicellular growth and its dysregulation can cause disease. While approximately 44 divisions are needed to produce without death all 10^13 cells in the human body, current methods are limited to count 10 cell divisions in vivo across diverse mammalian cell types. Here we introduce the DivisionCounter, a method to count cell division in vivo over large division ranges (approx 70 divisions) using an easy fluorescence readout. We demonstrate that the DivisionCounter accurately measures the average cell division count of cells both in vitro and in vivo. Its use revealed that leukemia tumor division rates are independent of the organ specific microenvironment and CAR T cell treatment, providing an estimate of tumor death rates in vivo. The DivisionCounter method holds unique potential for quantifying contributions of cell division, death, and migration to the growth of healthy and pathological mammalian tissues.