Monday, 26 August 2013

GATA-3 regulates the self-renewal of hematopoietic stem cells

Stem cell researchers at the Princess Margaret Cancer Centre made an announcement today, saying they have discovered that the gene GATA3 plays an important role in how hematopoietic stem cells (HSCs) renew themselves, a finding that advances the quest to expand these cells in the lab for clinical use in bone marrow transplantation, a life-saving procedure for thousands of patients each and every year.

The study, published online today in Nature Immunology, provides an important piece in the puzzle of understanding the mechanisms that govern the blood stem cell self-renewal process, explains principal investigator Norman Iscove, Senior Scientist at the Princess Margaret, University Health Network (UHN). Dr. Iscove is also an investigator at UHN's McEwen Centre for Regenerative Medicine and a Professor in the Faculty of Medicine, University of Toronto.

"Researchers have known for a long time that stem cells can increase their numbers in the body through self-renewal; however, it has proven very difficult to establish conditions for self-renewal in the laboratory," said Dr. Iscove.

Indeed, he explains, the quest to do so has been a holy grail for stem cell researchers because the very effectiveness, safety and availability of hematopoietic stem cell transplants depend on the number of stem HSCs available to transplant.

In the lab and using genetically engineered mice, Iscove's team zeroed in on GATA3 and determined that interfering with its function causes stem cells to increase their self-renewal rate and thereby results in increased numbers of stem cells. Dr. Iscove expects scientists will be able to use this new information to improve their ability to grow increased numbers of blood stem cells for use in bone marrow transplantation and possibly, gene therapy.

Dr. Iscove believes their research to be a new page in the growing volume of stem cell science that began in 1961 with the ground-breaking discovery of blood-forming stem cells by Drs. James Till and the late Ernest McCulloch.

Their discovery changed the course of cancer research and laid the foundation for bone marrow transplantation in leukemia patients, as well as for many other types of current disease research. 

The research published today was funded by the Terry Fox Foundation, the Canadian Cancer Society Research Institute, the Canadian Institutes of Health Research, the Stem Cell Network, the McEwen Centre for Regenerative Medicine, The Princess Margaret Cancer Foundation, The Campbell Family Institute for Cancer Research and the Ontario Ministry of Health and Long-term care.

Catherine Frelin, Robert Herrington, Salima Janmohamed, Mary Barbara, Gary Tran, Christopher J Paige, Patricia Benveniste, Juan-Carlos Zuñiga-Pflücker, Abdallah Souabni, Meinrad Busslinger & Norman N Iscove (2013). GATA-3 regulates the self-renewal of long-term hematopoietic stem cells Nature DOI: 10.1038/ni.2692

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