A recent study has uncovered significant new insights into the specialization of blood stem cells in humans, challenging long-held beliefs in the field of hematology. Researchers led by Tetsuichi Yoshizato from the Department of Medicine, Huddinge have found that not all blood stem cells contribute equally to blood cell production, suggesting a more complex landscape of blood cell formation than previously understood.
For decades, scientists maintained that all blood-forming stem cells were capable of producing every type of blood and immune cell. However, recent studies in mice indicated a different reality, showing that some stem cells do not replenish all blood cell lineages. In this groundbreaking research, published in Nature Genetics on March 15, 2025, the team was able to explore this phenomenon in humans for the first time.
Using unique DNA mutations as natural “barcodes,” the researchers traced the contributions of individual blood stem cells to various blood cell types in healthy elderly individuals. Yoshizato remarked, “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 revealed that these differences in stem cell behavior are not linked to specific gene mutations. Instead, they appear to be intrinsic properties of the stem cells themselves. This revelation marks a significant departure from previous assumptions about blood stem cell functionality.
Implications for Medical Treatment
The implications of these findings are profound for medical science. Understanding the specialization of blood stem cells could enhance strategies for optimizing blood cell production following procedures such as bone marrow transplantation and chemotherapy. Sten Eirik Jacobsen, Professor of Stem Cell Biology and Regenerative Medicine at the same institution, noted, “We were excited when we realized that we could use naturally occurring mutations in human blood stem cells to fate map their lineage contribution.”
Moreover, the researchers observed that the blood lineage replenishment patterns remain stable even after transplantation, indicating a programmed stability in stem cell behavior. Advanced retrospective phylogenetic analyses confirmed that most stem cells maintain their lineage patterns for decades, although a subset may become more restricted as individuals age. Serial bone marrow analyses conducted over a five-year period reinforced this long-term stability.
These discoveries hold significant potential for improving treatment strategies for diseases that disrupt blood cell production. Additionally, understanding how normal stem cells can transform into cancer stem cells will be essential in developing targeted therapies for blood cancers.
As researchers continue to explore the nuances of blood stem cell behavior, the hope is that these insights will lead to more effective treatments for patients facing challenges related to blood cell production and cancer. The study represents a pivotal point in hematological research, paving the way for future innovations in the field.
For more information, reference the study: Tetsuichi Yoshizato et al, Stable clonal contribution of lineage-restricted stem cells to human hematopoiesis, Nature Genetics (2025). DOI: 10.1038/s41588-025-02405-w.
