Researchers have unveiled significant findings regarding blood stem cells in humans, challenging long-held beliefs about their functionality. A study published in March 2025 in the journal Nature Genetics reveals that not all blood stem cells contribute equally to the production of blood cells. This research, led by Tetsuichi Yoshizato from the Department of Medicine, Huddinge, provides new insights into how these crucial cells operate and their implications for treating blood disorders.
Each second, millions of blood cells are generated in the human body, with approximately 90% of daily cell replacements being blood cells. These include vital components such as red blood cells, which transport oxygen, platelets that facilitate blood clotting, and immune cells that defend against infections. Blood-forming stem cells in the bone marrow are responsible for this continuous replenishment. While these stem cells are essential for lifelong blood cell production and crucial in medical applications like bone marrow transplants and chemotherapy recovery, they also pose risks. Each blood stem cell accumulates around 20 DNA mutations annually, with rare mutations potentially leading to common blood cancers.
For many years, scientists assumed that all blood stem cells were capable of producing every type of blood and immune cell. Recent mouse studies, however, indicated otherwise, suggesting that some stem cells do not replenish all blood lineages. The latest research shifts this focus to humans, where researchers utilized DNA mutations as natural “barcodes” to trace stem cell contributions to different blood cell types.
Yoshizato stated, “We were able to explore this phenomenon for the first time in humans. Our findings were striking: human blood-forming stem cells behave much like those in mice. Some stem cells contribute to all blood lineages, while others are more specialized.” The study found that differences in stem cell functionality were not associated with specific gene mutations, indicating that lineage bias is an intrinsic property of the stem cells themselves.
Co-author Sten Eirik Jacobsen, Professor of Stem Cell Biology and Regenerative Medicine at the same institution, expressed enthusiasm for the findings. “We were excited when we realized that we could use naturally occurring mutations in human blood stem cells to fate map their lineage contribution,” he remarked. The stable lineage patterns observed in the study persisted even after transplantation, demonstrating that these traits are inherently programmed.
Employing advanced retrospective phylogenetic analysis, researchers confirmed that most stem cells maintain their lineage contributions over decades, although some exhibit more restricted functionality as they age. Serial analyses of bone marrow over a five-year period reinforced the notion of long-term stability in these patterns.
The implications of these discoveries for medicine are considerable. They may enhance blood cell production strategies following bone marrow transplantation or chemotherapy, ultimately improving treatment for conditions where blood cell production is compromised. Furthermore, understanding how normal stem cells can evolve into cancer stem cells will be vital for developing targeted blood cancer therapies.
For more information, see the article by Tetsuichi Yoshizato et al., titled “Stable clonal contribution of lineage-restricted stem cells to human hematopoiesis,” published in Nature Genetics.
