Abstract

Multi-isotope imaging mass spectrometry (MIMS) is a new and generally applicable method for the study of DNA replication, lipid and protein turnover and cell fate in animals and humans. In a proof-of-principle study, MIMS was used to test the 'immortal strand hypothesis', which proposes that stem cells maintain a master genetic template that is protected from cancer-causing mutations. The hypothesis remains hotly debated, in part because of the difficulties involved in testing it experimentally. Stable isotope incorporation was viewed and measured by MIMS in mammalian intestinal cell division, Drosophila melanogaster lipid metabolism and human lymphopoiesis. In the auditory system, the mechanosensory hair cells of the inner ear convert sound-induced vibrations into electrical signals. The apical surface of a hair cell consists of stereocilia with a core of actin filaments that function as mechanosensors. It has been suggested that these actin filaments are replaced within two to three days by a treadmilling process. Using the newly developed multi-isotope imaging mass spectrometry (MIMS) technique, Zhang et al. quantify protein turnover in hair-cell stereocilia in vivo and find that turnover is slow throughout the stereocilia, except for the tip region, and does not involve a treadmilling process.

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