"We found that during development, ERG was not needed for the original blood stem cells to be made, or to produce mature blood cells," Dr Taoudi said. "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 the 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," Dr Taoudi said. "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."
Dr Taoudi said that although the finding had promise for the future therapeutic use of blood stem cells, there was still a lot of work to be done.
"We have found part of the pathway required for the expansion of blood stem cells under normal conditions, but from a translation perspective, we still need to establish whether increasing expression of these genes will actually lead to expansion in a culture dish," he said.
|Contact: Penny Fannin|
Walter and Eliza Hall Institute