Finding a simple method for the reliable identification of haematopoietic stem cells (HSCs) has proved elusive. Now, a report in Cell shows that, in mice, long-term-reconstituting HSCs (LT-HSCs) — which have extensive self-renewal capacity (a hallmark of stem cells) — can be precisely distinguished from closely related haematopoietic progenitors by their cell-surface expression of members of the signalling lymphocytic activation molecule (SLAM) family.

At present, mouse HSCs are identified on the basis of their expression of a complex combination of cell-surface markers, many of which are strain specific or activation dependent. Furthermore, using the most common combination of markers, only ∼20% of the cells isolated have self-renewal capacity and thereby allow long-term reconstitution of all haematopoietic-cell lineages following transplantation. So, Kiel and colleagues set out to improve our ability to reliably identify LT-HSCs.

They first carried out gene-expression profiling of highly purified populations of LT-HSCs and multipotent progenitors (MPPs); MPPs give rise to multiple haematopoietic-cell lineages but do so only transiently, as they do not have self-renewal capacity. Of the 27 genes that were identified to be upregulated in LT-HSCs compared with MPPs, the SLAM-family member CD150 (also known as SLAM) was a good candidate for identifying LT-HSCs because of its cell-surface expression. Next, the authors transplanted CD150+ or CD150− bone-marrow cells into irradiated mice. The CD150+ cell population provided long-term reconstitution of multiple haematopoietic-cell lineages, whereas the CD150− cell population could do so only transiently.

On subsequently examining the expression of other SLAM-family molecules, the authors found that three members were differentially expressed by progenitors with different capacities for reconstitution — LT-HSCs were CD48−CD150+CD244−, MPPs were CD48−CD150−CD244+, and most restricted progenitors were CD48+CD150−CD244+ — and this expression pattern was conserved across different mouse strains.

SLAM-family members are known to regulate the activation and proliferation of lymphocytes, but they have not previously been shown to be expressed by haematopoietic progenitors. The ability to identify populations of haematopoietic progenitors on the basis of the combination of SLAM-family molecules that they express provides a simple, broadly applicable tool for isolating LT-HSCs and for studying their regulation and anatomical localization. If this differential expression is conserved across species, then it has potential for improving the success of HSC transplantation in humans.