Deeply dormant blood stem cells identified in mice, marked by EPCR

A team at the German Cancer Research Center (DKFZ) and the HI-STEM Stem Cell Institute has described a subset of blood stem cells in mice that remain dormant for far longer than conventional ones. The cells carry the surface protein EPCR but lack CD150, a marker that has long been used to identify blood stem cells. The work, led by Andreas Trumpp with first author Dawn Lin, appears in Cell Stem Cell.

A population hiding in plain sight

Blood stem cells in the bone marrow replenish the billions of blood cells the body produces each day. To avoid exhausting their capacity, many of them spend long periods in a quiescent state and divide only when the body demands it.

Researchers typically identify these cells with surface markers, and CD150 is among the most widely used. Cells without it were therefore often not counted as blood stem cells. The new study shows that, among these CD150-negative cells, a distinct group can be recognised by EPCR expression. These cells behave as long-term blood stem cells and are unusually deeply dormant.

Months of quiescence

The difference in dormancy was measurable. After more than 200 days in mice, only about 2% of conventional blood stem cells still showed a quiescence marker. Among the newly characterised cells, roughly 10% to 15% were still positive.

Inflammatory signals commonly rouse blood stem cells so that the body can make more immune cells, but repeated activation depletes the reserve. In the mice studied, the EPCR-positive population reacted to inflammatory stimuli far more cautiously than conventional blood stem cells did. The authors suggest this restraint may help the cells preserve their regenerative capacity over a lifetime.

Different subsets, different leanings

The two groups also differ in the cells they tend to produce. The CD150-positive stem cells lean towards red blood cells and platelets. The deeply dormant cells show a greater tendency to generate immune cells, particularly lymphocytes.

Both groups can nonetheless give rise to all major blood cell types. Transplantation experiments in mice confirmed this: even single cells from the new population produced every blood lineage and sustained it long term, and this capacity persisted through serial transplantation, a stringent test of self-renewal.

“Blood stem cells do not constitute a uniform cell population,” Lin says, pointing to subpopulations with distinct properties and functions.

Why it matters, and what is unknown

For researchers, the finding suggests that CD150-based definitions may have excluded a functionally important reserve, which could affect how stem cell populations are isolated, counted and compared. It also adds to the case that apparent heterogeneity in blood stem cells reflects real functional specialisation rather than noise.

Trumpp notes that blood stem cells underpin transplants used to treat leukaemias and other severe blood disorders. Understanding how some remain functional into old age could, he says, help improve such therapies and counter the decline of blood and immune function with age. These are prospective applications rather than demonstrated outcomes.

The key limitation is that all the evidence so far comes from mice. It has not been shown that an equivalent, particularly long-lived population exists in humans. Trumpp says the group already has initial evidence and that testing this is the next project.

The paper is Lin et al., “EPCR expression marks CD150neg deeply dormant long-term hematopoietic stem cells”, Cell Stem Cell (2026), DOI: 10.1016/j.stem.2026.09.016.

Source: Stem cells in deep sleep may point to a secret reserve for lifelong blood renewal (Phys.org, 3 November 2026).

Image: AI-generated illustration.