Research conducted by scientists at the Department of Medicine, Huddinge, has revealed significant insights into the behavior of blood stem cells in humans. This study, published in the journal Nature Genetics on March 15, 2025, indicates that blood-forming stem cells exhibit a surprising level of specialization, challenging long-held beliefs about their functionality.
Every second, millions of blood cells are generated in the human body. Approximately 90% of these cells are replaced daily, comprising red blood cells that transport oxygen, platelets for clotting, and immune cells that defend against infections. Due to their short lifespan, these cells need continuous replenishment, a task managed by blood-forming stem cells located in the bone marrow. These cells are critical not only for lifelong blood production but also for medical treatments such as bone marrow transplantation and recovery following chemotherapy.
Despite their importance, blood stem cells present a “dark side.” Over a lifetime, each stem cell accumulates about 20 DNA mutations annually. While most mutations are benign, certain stem cells can become the source of prevalent blood cancers. Understanding the functioning of these cells is, therefore, crucial for developing effective cancer treatments.
New Findings on Stem Cell Specialization
For decades, researchers believed that all blood stem cells were capable of producing every type of blood and immune cell. However, recent studies conducted in mice indicated otherwise, suggesting that some stem cells do not contribute to all blood cell lineages. Lead researcher Tetsuichi Yoshizato stated, “In our latest study, we were able to explore this phenomenon for the first time in humans. Each blood stem cell accumulates unique DNA mutations throughout life, allowing us to use the mutations as natural ‘barcodes’ to trace the stem cell contribution to different blood cell types in healthy elderly individuals.”
The findings demonstrated that human blood-forming stem cells behave similarly to those observed in mice. Certain stem cells contribute to all blood lineages, while others are more specialized. Notably, these differences were not associated with specific gene mutations, indicating that the lineage bias is an intrinsic characteristic of the stem cells themselves.
Implications for Medical Treatments
Professor Sten Eirik Jacobsen, head of the Hematopoietic Stem Cell Biology Group, expressed enthusiasm about the study’s implications. “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 noted. The research revealed that even after transplantation, the patterns of stem cell contribution remained stable and intrinsically programmed.
Advanced phylogenetic analysis confirmed that the majority of stem cells maintain their lineage patterns for decades, although some show increased restriction with age. Furthermore, serial analyses of bone marrow over a five-year period reinforced the notion of long-term stability in these lineage patterns.
These discoveries hold considerable promise for medical applications. Understanding the specialization of blood stem cells could enhance blood cell production following procedures like bone marrow transplantation or chemotherapy. Additionally, insights into which normal stem cells can evolve into cancer stem cells will be pivotal in formulating targeted therapies against various blood cancers.
The ongoing research into the complexities of blood stem cells not only expands the scientific community’s understanding but also paves the way for innovative treatment strategies in the future.
