A group of scientists from the Centre for Genomic Regulation (CRG) in Barcelona and Columbia University in New York City has discovered a protein that is crucial for expanding the usually scarce, life-saving blood stem cells.
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The finding may result in new techniques for growing a large number of such stem cells, both outside and inside the human body. This is presently one of the greatest restrictions when it comes to using these stem cells in a wide range of medical procedures, right from the treatment of blood cancers to genetic blood disorders that need bone marrow transplantation. The results were recently reported in the Cell Reports journal.
Hematopoietic stem cells (HSCs) account for the continuous renewal of blood and they generate an unlimited number of new cells every day. These cells have an infinite ability to regenerate themselves for the whole lifetime of an organism, resulting in all types of blood cells, such as cells that constitute the human immune systems.
HSCs show excellent promise in treating incurable cancers, inherited blood disorders, and autoimmune diseases. But only 1 in 2500 cells in the blood marrow is actually HSCs, and this shortage restricts their application in medical procedures.
One method to obtain more HSCs is by increasing the current number identified in the cord blood, bone marrow, or circulating blood. The second method is by reprogramming other types of blood stem cells such that they attain some of the self-renewing features that are typical of HSCs.
An algorithm, known as VIPER, was used by the team to detect proteins that can reprogram other types of blood stem cells. Among the eight promising candidates spotted by the algorithm, only one—a gene called BAZ2B—was able to considerably increase the amount of HSCs from the umbilical cord blood.
The BAZ2B gene reprogramed the blood stem cells to an HSC-like state by reorganizing their chromatin, revealing special genomic regions that could not be accessed before. The resulting cells effectively transplanted into the bone marrow of immunocompromised mice and renewed the tissue growth.
The scarcity of hematopoietic stem cells is one of the biggest barriers to the development of new and improved treatments. Our findings are exciting because we have found a way of boosting their numbers after activating just one factor. Yielding more of these life-saving stem cells will benefit a variety of different patients in the long-term.”
Pia Cosma, Study Author and ICREA Research Professor, Center for Genomic Regulation
Cosma is also the Group Leader at CRG.
“It is really exciting to see that the methodologies we have developed to discover the proteins that implement and maintain the malignant state of cancer cells can also be used to identify key players in normal human physiology, including proteins that can help fight other diseases,” stated Andea Califano—the Clyde and Helen Wu Professor of Chemical and Systems Biology at Columbia University Medical Center.
Remarkably, the proteins that are best suited to the VIPER methodology are exactly those that control human developmental processes, such as blood differentiation and regeneration, thus opening up new exciting avenues in regenerative medicine.”
Andea Califano, Clyde and Helen Wu Professor of Chemical and Systems Biology, Columbia University Medical Center
Arumugam, K., et al. (2020) The Master Regulator Protein BAZ2B Can Reprogram Human Hematopoietic Lineage-Committed Progenitors into a Multipotent State. Cell Reports. doi.org/10.1016/j.celrep.2020.108474.