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Saturday, November 23, 2024

Scientists discover key protein enabling lab-grown human blood stem cell renewal

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Dr. Michael Drake, President | Official website

Dr. Michael Drake, President | Official website

UCLA scientists have identified a protein that plays a critical role in regulating human blood stem cell self-renewal by helping them sense and interpret signals from their environment. The study, published in Nature, brings researchers one step closer to developing methods to expand blood stem cells in a lab dish, which could make lifesaving transplants of these cells more available and increase the safety of blood stem cell-based treatments, such as gene therapies.

Blood stem cells, also known as hematopoietic stem cells, have the ability to make copies of themselves via a process called self-renewal and can differentiate to produce all the blood and immune cells found in the body. For decades, transplants of these cells have been used as lifesaving treatments for blood cancers such as leukemia and various other blood and immune disorders.

However, blood stem cell transplants have significant limitations. Finding a compatible donor can be difficult, particularly for people of non-European ancestry, and the number of stem cells available for transplant can be too low to safely treat a person’s disease.

These limitations persist because blood stem cells that have been removed from the body and placed in a lab dish quickly lose their ability to self-renew. After decades of research, scientists have come close to solving this problem.

“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,” said Dr. Hanna Mikkola, senior author of the new study and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

To pinpoint the missing piece that prevents these blood stem cell-like cells from being fully functional, Julia Aguade Gorgorio analyzed sequencing data to identify genes that are silenced when blood stem cells are placed in a lab dish. One such gene, MYCT1, which encodes a protein by the same name, stood out as being essential to these cells’ self-renewal capacity.

They found that MYCT1 regulates a process called endocytosis, which plays a key role in how blood stem cells take in signals from their environment that tell them when to self-renew when to differentiate and when to be quiet.

“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,” said Aguade Gorgorio. “Without this protein the signals from the cell's environment turn from whispers into screams and the cell becomes stressed out.”

The researchers compare MYCT1 to sensors in modern cars that monitor nearby activity selectively relaying crucial information at appropriate times aiding decisions like turning or changing lanes safely. Without MYCT1 blood stems resemble anxious drivers lost without guidance.

Next researchers used viral vectors reintroducing MYCT1 restoring its presence allowing self-renewal making expanded functional post-transplant mouse models effective.

As next steps investigating why silencing occurs preventing safer clinical settings without viral vectors will be pursued.

“If we find ways maintaining expression maximizing advances improving accessibility effectiveness affordability,” concluded Mikkola professor molecular developmental biology UCLA College member Health Jonsson Comprehensive Cancer Center.

Support provided National Institutes Health Swiss National Science Foundation European Molecular Biology Organization Jonsson Cancer Center Foundation James B Pendleton Charitable Trust McCarthy Family Foundation California Institute Regenerative Medicine AIDS Institute Board Governors Cedars-Sinai Medical Center Royal Society Wellcome Trust Broad Stem Cell Research Training Program.

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