Gene `switches blood renewal`

Key gene in blood cell self-renewal identified.

Washington: Scientists claim to have identified a key gene in blood cell self-renewal, a major step towards culturing a supply of blood cells in the laboratory.

An international team, led by the Walter and Eliza Hall Institute, has discovered that the `Erg` gene is vitally important to blood stem cells` unique ability to self-renew, providing new opportunities to use blood stem cells for tissue repair, transplantation and other therapeutic applications.

"One of the key features of blood stem cells, one that could be exploited for therapeutic use, is their ability to regenerate or renew themselves. However, relatively little is known about how this occurs, or the molecular pathways that control regeneration," Samir Taoudi, who led the team, said.

Blood stem cells are required to produce and maintain the blood system throughout an organism`s lifetime. They are multipotent cells, meaning they are able to form any cell of
the blood system, and they self-renew, so they are a source of endless supply.

However, one major barrier to their therapeutic use is that the cells can only be isolated in numbers too low for practical use and efforts to expand the number of cells often causes them to turn into more mature cells.

"At the moment, if you take stem cells from a person and try to expand them, many of the stem cells lose their ability to regenerate," Dr Taoudi said.

Dr Taoudi added: "The practical aim of our research is to find ways in which you could take stem cells collected from bone marrow or cord blood and `switch on` expression of
particular sets of genes, encouraging the stem cells to expand essentially creating your endless supply of blood stem cells.

"We found that during development, ERG was not needed for the original blood stem cells to be made, or to produce mature blood cells.

"But without ERG, these new blood stem cells rapidly decreased as they divided to produce more blood, so that they were almost completely exhausted by the time mouse was born."

Further testing revealed that two other genes important in embryonic development, GATA2 and RUNX1, were controlled by ERG at the blood producing stage of development.

"These genes are called transcription factors, they are the `switches` that turn on and off other genes.

Individually, these genes are not essential for regeneration, but if you lose both, the stem cells are quickly exhausted.

“This is a key part of the puzzle, but we will continue to work to find out how these genes directly control self-renewal, and the signals that actually tell the stem cell to regenerate," he said.

The findings have been published in the `Genes and Development` journal.