Haematopoietic stem cell quiescence exposed using mitochondrial membrane potential

Quiescence is a fundamental property of haematopoietic stem cells (HSCs). Despite the importance of quiescence in predicting the potency of HSCs, tools that measure routinely the degree of quiescence or select for quiescent HSCs have been lacking. This Commentary discusses recent findings that address this fundamental gap in the HSC toolbox.

Highly purified, phenotypically-defined HSCs are heterogeneous in their mitochondrial membrane potential (MMP). The lowest MMP subsets are enriched in greatly quiescent HSCs with the highest potency within the purified HSC population. MMP provides an intrinsic probe to select HSC subsets with unique cell cycle properties and distinct stem cell potential. Using this approach, new and unanticipated metabolic properties of quiescent HSCs' exit have been discovered. This methodology may improve the mechanistic understanding, of HSCs' exit from and entry to, quiescence.

Selecting HSCs using MMP is likely to lead to discoveries of new HSC properties, may improve the ex vivo maintenance of HSCs and has implications for the clinic, including for improving HSC transplantations.