UCLA scientists have discovered a protein crucial for blood stem cell self-renewal, potentially transforming the availability and safety of stem cell transplants and gene therapies.
In a groundbreaking study published in Nature, scientists from UCLA have uncovered a crucial protein, MYCT1, that could revolutionize blood stem cell transplants and gene therapies.
UCLA researchers have identified MYCT1’s essential role in regulating blood stem cell self-renewal, marking an advancement decades in the making. MYCT1 enables stem cells to sense and respond to their environment, a process critical for their longevity and effectiveness.
“We’ve figured out how to produce cells that look just like blood stem cells and have all of their hallmarks, but when these cells are used in transplants, many of them still don’t work; there’s something missing,” Hanna Mikkola, senior author of the study and a member of UCLA’s Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, said in a news release.
Blood stem cells, or hematopoietic stem cells, possess the unique ability to self-renew and produce all blood and immune cells in the body. For years, their transplants have offered lifesaving treatments for blood cancers like leukemia and various immune disorders. However, these treatments face limitations — finding compatible donors and maintaining stem cell potency outside the body.
Researchers attribute these hurdles to the difficulty in sustaining stem cell self-renewal in lab conditions. When blood stem cells are cultured, they quickly lose their regenerative capabilities. To pinpoint the cause, the study’s first author, Julia Aguade Gorgorio, analyzed gene sequences silenced during culture, identifying MYCT1 as a key player.
“When cells perceive a signal, they have to internalize it and process it; MYCT1 controls how fast and how efficiently blood stem cells perceive these signals,” Aguade Gorgorio, an assistant project scientist in the Mikkola lab, said in the news release.
Without MYCT1, the signals necessary for self-renewal become overwhelming, leading to stress and dysfunction in the cells.
The team likens MYCT1 to the advanced sensors found in modern vehicles, which selectively alert drivers to critical information. Without these sensors, drivers might become overwhelmed and disoriented — much like how stem cells react without MYCT1.
Introducing MYCT1 back into stem cells using a viral vector, researchers observed restored self-renewal capabilities in cultured blood stem cells. These rejuvenated cells successfully functioned when transplanted into mouse models, demonstrating potential for human application.
“If we can find a way to maintain MYCT1 expression in blood stem cells in culture and after transplant, it will open the door to maximize all these other remarkable advances in the field,” added Mikkola, also a professor at UCLA’s College and a member of the Jonsson Comprehensive Cancer Center.
This discovery could not only enhance the efficiency of blood stem cell transplants but also significantly improve the safety and accessibility of gene therapy treatments.
Future research will focus on understanding why MYCT1 is silenced and developing methods to maintain its expression in blood stem cells without relying on viral vectors. This approach promises to amplify the impact of existing scientific advancements and make treatments more feasible and affordable.
This pioneering work received support from various national and international foundations, including the National Institutes of Health, the European Molecular Biology Organization and the California Institute for Regenerative Medicine. The research signifies a pivotal step towards transforming the landscape of stem cell therapy and regenerative medicine, offering new hope for those afflicted by severe blood and immune disorders.