Science Briefs, Transcription Factors play a role in maintaining Blood Stem Cells
It’s long been a mystery as to how hematopoietic stem cells (HSC), or blood stem cells, differentiate into the various blood cells and regenerate themselves from the earliest stages of development throughout life.
- Now researchers at the Walter and Eliza Hall Institute (WEHI) have revealed the role of the Erg gene.
It was known there is a host of genes that play a role in differentiation and regeneration, but it was not known precisely what role the Erg gene played, or if it was even required. Past experiments have shown that the lack of the Erg gene in mice and zebra fish didn’t prevent blood cells from being created.
- Erg is not involved in differentiation;
- However, without Erg, the HSCs don’t renew themselves and eventually become exhausted;
- They found that Erg regulates 2 other genes, Gata2 and Runx1, and these are involved in maintaining the HSCs.
Individually, these genes are not essential for regeneration, but if you lose both, the stem cells are quickly exhausted. The key to the puzzle is how these genes directly control self-renewal and the signals that actually tell the stem cell to regenerate.
- The study, published in Genes and Development, was funded by the National Health and Medical Research Council, the Australian Cancer Research Foundation, the Australian Stem Cell Centre, the Australian Research Council, the Sylvia and Charles Viertel Charitable Foundation and the Victorian Government. (HWM and TDean, AU Life Scientist)
The Bottom Line: There is little is known about the molecular pathways that specifically control regeneration. HSCs are multipotent, so they can become any of the other blood cells, although they can normally only be isolated in numbers too small for therapeutic use. These genes are called transcription factors; they are the ‘switches’ that turn on and off other genes. But, when they are isolated, they often lose their ability to differentiate into other 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. The practical aim of this research is to find ways stem cells are collected from bone marrow or cord blood and ‘switch on’ expression of particular sets of genes, encouraging the stem cells to expand, thus creating an endless supply of blood stem cells. The discovery has tissue repair therapy, transplantations and therapeutic implications.