Small, Yet Powerful Mitochondria and Blood Stem Cells
Two recent studies of blood stem cells highlight the importance of cellular components called mitochondria in determining how these cells function. Mitochondria are referred to as the “powerhouses” of the cell because these small organelles take energy that is ingested in the form of sugars or fats and convert it to fuel for the cell in a process called respiration. Blood stem cells (also called hematopoietic stem cells) have the potential to self-renew into two identical daughter stem cells or give rise (mature) to specialized cell types: red blood cells, white blood cells, or platelets. Scientists have sought to discover the cellular players that tip the balance in favor of self-renewal versus maturation.
In one report, scientists discovered that blood stem cells that retain the capacity to self-renew have a protein on their cell surface called Tie2, a feature distinguishing them from blood stem cells that may be on a path to become mature blood cells. When examining human and mouse blood stem cells with and without Tie2, they found that those with Tie2 have superior ability to grow and repeatedly give rise to new daughter stem cells over longer periods of time in the laboratory, creating many generations of blood stem cells. In experiments in mice, blood stem cells with surface Tie2 were also more effective at migrating to the bone marrow, where they normally reside and self-renew. Further analysis of mouse Tie2-containing blood stem cells showed that these cells “turn on” several genes involved in the degradation of mitochondria, which helps cells remain healthy by selectively removing damaged mitochondria. Based on additional experiments, the researchers proposed that the process of mitochondrial clearance may be a key determinant that commits these cells to the self-renewal pathway.
A second advance assessed whether intact, functional mitochondrial respiration is required for the function of mouse fetal and adult blood stem cells. The investigators found that deficiency in a protein component of the mitochondrial respiration process, called RISP, resulted in a mouse fetus that developed fewer red blood cells than normal and subsequently died. In addition to the lack of red blood cells, the late-stage mouse fetus contained fewer white blood cells and platelets—an indication that the blood stem cells were unable to mature into other critical blood cells. Another set of experiments confirmed that intact mitochondrial respiration is also essential for adult mouse blood stem cell functions. In contrast to normal adult blood stem cells, those lacking RISP initially generated more cells, but soon these cells died—resulting in an inadequate number of blood stem cells to self-renew or mature into specialized blood cells. These findings, in mice, suggest that mitochondrial respiration is required for normal blood stem cell function.
These two studies serve to underscore the significance of mitochondrial activity in normal blood stem cell function. Approaches to engineer these pathways may enable investigators to direct these cells to undergo self-renewal or maturation, which could be useful for future study of these important cells and for potential therapeutic strategies.