Bone marrow stem cells Regulatory Mechanisms

A recent study has uncovered a critical mechanism governing the function of bone marrow stem cells, providing fresh insight into the fundamentals of stem cell biology and perhaps leading to novel therapeutic approaches.

Two molecules have been found by Eric So, Professor and Chair in Leukaemia Biology at the Comprehensive Cancer Centre, and his research team to regulate the phases during which bone marrow stem cells undergo rest and recovery as well as their proliferative phases. Later on, the scientists identified an enzyme that mediates these compounds’ actions. Their findings provide a new avenue for potential therapies, as bone marrow stem cell transplantation has been the cornerstone treatment for a wide range of blood malignancies.

The Blood Journal publishes the research.

“Given the critical functions of stem cells in bone marrow transplant and cancer biology, identification of a new druggable pathway not only will help to understand the stem cell biology better but also facilitates the development of more effective therapeutics in the future,” said So.

Hematopoietic stem cells (HSCs) are a rare population of self-renewing stem cells that mostly reside in the bone marrow and are essential for the blood system’s lifelong renewal. Because HSCs can differentiate into other blood cells, including red blood cells, white blood cells, and platelets, as necessary, they are essential.

HSCs can be either active or dormant. During their quiescent state, they are shielded from external stresses and have the opportunity to relax, avoiding fatigue. To refill the blood system in response to issues like infection, blood loss, and other challenges, dormant HSCs must reactivate to proliferate.

Stem cells must be kept safe and dormant while also having the ability to reproduce and react to stress when necessary. This requires a complex and delicate balancing act. To treat many deadly diseases, including cancer, bone marrow transplantation is a life-saving treatment that depends heavily on this equilibrium. In a similar vein, cancer stem cells that maintain the illness and trigger relapses depend on equilibrium. Therefore, to create effective treatments, it is essential to comprehend this process.

In the study, Professor So and his colleagues discovered that two crucial molecules—Hoxa9 and b-catenin—cooperate closely to protect these two characteristics in regulating the active and inactive states of HSCs. The researchers discovered that a robust system to safeguard our blood production is provided by one molecule’s ability to make up for the other’s inactivity.

These discoveries have already contributed to a deeper understanding of the fundamental concepts of stem cell biology among researchers. But later on, Professor So and his team discovered a crucial enzyme called PRMT1 that mediates the activity of b-catenin and Hoxa9. Since clinicians can currently modify PRMT1 in the clinic, gaining a better knowledge of this biological mechanism may open up new possibilities for creating effective stem cell therapies.

For more information: Hematopoietic stem cell quiescence and DNA replication dynamics maintained by the resilient β-catenin/Hoxa9/Prmt1 axis, Blood Journal (2024), DOI: 10.1182/blood.2023022082