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Collaborative work between the Nerlov and Vyas groups in the MRC Molecular Haematology Unit within the WIMM, published this week in Science Immunology, has identified platelet-biased blood stem cells in humans for the first time. This demonstrates that this subtype of stem cells is a conserved feature of mammalian evolution.
Blood stem cells, or haematopoietic stem cells (HSCs), produce new blood cells, which the human body needs to maintain oxygen transport, blood clotting and immunity to invading pathogens. HSCs are also an important cell type in bone marrow transplantation, which is a form of treatment for blood cancers and inherited genetic diseases - since 1957, more than 1.5 million patients have received such bone marrow transplants.
Much of what is known about HSCs comes from studies in mice. In particular, work from the Nerlov group at the Weatherall Institute of Molecular Medicine (WIMM) over the last decade has shown that there are two fundamentally different types of HSC:
- Multi-lineage HSCs - that make all the different types of blood cells
- Platelet-biased HSCs - that mainly make platelets (blood cells that help clots to form to stop bleeding)
In a young organism, platelet-biased HSCs are rare, but with age they become the predominant type. This leads to decreased production of other blood cells, in particular cells called lymphocytes that are important for defending against new viruses (e.g. COVID-19), but also against other microbes and cancers. The Nerlov group also found that in old mice eliminating platelet-biased HSCs could increase lymphocyte production, paving the way for therapies to improve immunity in older organisms. However, before the results of this study, we did not know if the same HSC subtypes existed in humans.
By combining methods to track single human HSCs (called in vivo barcoding) with detailed molecular characterisation of these single HSCs (a method called high-throughput single cell RNA sequencing), the Nerlov and Vyas groups identified human HSCs with the same molecular properties as mouse platelet-biased HSCs. They also showed that these human HSCs predominantly produced platelets. In addition, comparison of HSCs from young and old human bone marrow showed that the proportion of platelet-biased HSCs also increased with age in humans, as it did in mice.
Considerable efforts are being made to find ways to mitigate the adverse health impacts of ageing, and rejuvenation of the blood system has considerable potential in that area. Lead author, Professor Claus Nerlov said:
This work shows that one way forward could be by reducing the number of platelet-biased HSCs and increasing the number of multi-lineage HSCs to sustain more balanced blood production as we age. The conservation of HSC subtypes and the changes they undergo with age between mice and humans makes it more likely that rejuvenating strategies could first be developed and tested in mice before they are safely tested in humans.