High-Fidelity Quantification of Cell Cycle Activity with Multi-Isotope Imaging Mass Spectrometry

The quantification of cell cycle activity is a prerequisite to defining the dynamics and scope of organ development or regeneration. Multi-isotope imaging mass spectrometry (MIMS) merges stable isotope tracers with an imaging mass spectrometry platform called NanoSIMS, which can quantitatively measure the incorporation of stable isotope tracers with high precision in suborganelle domains. MIMS has been applied to quantify the dynamics of postnatal cardiogenesis and mammalian cardiomyocyte regeneration during aging or in response to injury. Here, we present an approach to the conduct of MIMS experiments, with an emphasis on the application to the field of cardiac regeneration; however, the approach is also applicable, with, at most, minor modifications to broader biological questions.