In two papers in this issue, Lechene and colleagues1,2 report the first use of an approach called multi-isotope imaging mass spectrometry (MIMS) in living organisms (see pages 516 and 520). This technique has outstanding resolution: it provides data in the sub-micrometre range, allowing analysis of structures as small as cellular regions.

MIMS involves labelling living tissues with stable isotopes. The isolated sample surface is then bombarded with a beam of ions, and the ejected 'secondary' ions are measured with a mass spectrometer to determine the sample's molecular composition. The technique can distinguish between ions of very similar mass, providing a precise measurement of isotope labels, which can be imaged simultaneously.

Credit: C. P. LECHENE AND COLLEAGUES

Lechene and co-workers used MIMS to test the immortal-strand hypothesis, which proposes that asymmetrically dividing stem cells also segregate their DNA asymmetrically. That is, the daughter cells that will remain stem cells retain the older DNA template, whereas those that are committed to differentiation inherit newly synthesized DNA strands. The authors disprove this proposal, showing that DNA strands segregate randomly in proliferating crypt cells of the mouse small intestine (pictured). This finding should further our understanding of tissue homeostasis.

The researchers also analysed protein turnover in the mechanosensory hair cells in the inner ear of frogs and mice. During most vertebrates' lifetime, hair cells are not replaced, but their degraded proteins are. One kind of structure within these cells is the stereocilia, each of which is made up of hundreds of filaments of the protein actin. Lechene and collaborators quantified actin turnover in both adult and neonatal hair cells and report that, with the exception of the filaments' tips, this protein's turnover is particularly slow throughout stereocilia. This observation differs from previous findings3 that stereocilium actin has a rapid turnover time. According to Lechene and co-authors, this discrepancy may be due to differences in experimental conditions between the two studies.

The team also demonstrates successful use of MIMS for human studies. They thus not only further prove the broad applicability of their technique, but also open the door to its use for investigations of metabolism and cell-lineage tracking in humans.