In the bone marrow of humans, hematopoietic stem cells play a crucial role in producing 500 billion new blood cells every day. These stem cells not only generate all types of blood cells but also regenerates themselves to ensure the smooth operation of blood production. However, as these stem cells age, they lose functionality, increasing the risk of aging-associated diseases, including blood cancers. Despite knowing that the risk of developing these diseases varies among individuals, little is known about how hematopoietic stem cells age differently between individuals. Jennifer Trowbridge and her colleagues conducted a study to investigate this issue by examining individual middle-aged mice on a single-cell level.
In their study, Trowbridge’s team discovered that despite being the same age, hematopoietic stem cells in the bone marrow of individual mice aged differently. They also found that the function of these stem cells could be predicted based on the activity of two growth factors, Kitl and Igf1, produced by mesenchymal stromal cells surrounding the stem cells in the bone marrow microenvironment. By profiling the RNA transcriptome in these surrounding cells, Trowbridge observed that the decline of these growth factors correlated with age-associated molecular programs in the stem cells. This variation in hematopoietic stem cells was markedly higher compared to other cells in the bone marrow, providing insight into the aging process at a cellular level.
Despite the controlled nature of the animal study, Trowbridge believes that in humans, who are genetically diverse and have varying lifestyles, variations in hematopoietic stem cell aging are likely to be even greater. While the study did not directly explore whether cellular aging of the stem cells triggers adverse health outcomes, Trowbridge suggests that these variations could play a role in a wide range of health outcomes for both mice and humans. Understanding how hematopoietic stem cells age differently between individuals could pave the way for personalized health approaches and targeted treatments for aging-related diseases.
The findings indicate that the amount of growth factors produced by surrounding mesenchymal stromal cells directly correlates with the declining function of hematopoietic stem cells. By studying individual mice on a single-cell level, Trowbridge’s team was able to observe the variations in stem cell aging and predict their function based on the activity of specific growth factors. This provides valuable insights into how aging affects hematopoietic stem cells and how different individuals may experience varied outcomes in terms of health and disease risk.
The study sheds light on the importance of understanding how hematopoietic stem cells age and lose functionality as individuals grow older. By identifying the role of growth factors produced by surrounding cells in the bone marrow microenvironment, researchers can gain insights into the aging process at a cellular level. This knowledge could potentially lead to the development of new therapies or interventions aimed at preserving the function of hematopoietic stem cells and reducing the risk of aging-associated diseases. Further research in this area may help in uncovering personalized approaches to healthcare and disease prevention based on individual differences in hematopoietic stem cell aging.