The pathway that allows blood stem cells to hibernate, and therefore repeatedly renew themselves, has been revealed.
Researchers at the German Cancer Centre (DKFZ) and the Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), both in Heidelberg, Germany, have found the factors involved in the blood stem cell hibernation of mice.
Professor Andreas Trumpp, one of the lead researchers and authors of the study, noted 'The dormancy is the prerequisite for this unique ability of stem cells', referring to the lifelong ability for the stem cells to self-renew. This capacity to continuously divide and regenerate is vital to health and survival, as it maintains protection against threats to the body such as blood loss, infection and inflammation over the course of the body's lifetime.
Although it had previously been found that a state of dormancy in blood stem cells is necessary to maintain this function, the process that lead to the cells entering this state was unclear. Now researchers at the DKFZ and HI-STEM have found the two factors involved.
Publishing their research in Nature Communications, they discovered that dormant blood stem cells in mice contain large amounts of the receptor protein neogenin-1 (neo-1) on their surface. In contrast, it was found that active blood stem cells within the mice did not. When the researchers genetically switched off the neo-1 receptor, the stem cells were no longer dormant. This led them to lose their ability to self-renew and they therefore aged prematurely.
The scientists also found that the signalling molecule netrin-1, produced by the blood vessels within the stem cell niche (the immediate surrounding area of stem cells), is responsible for binding to and activating the neo-1 receptor. When netrin-1 was reduced, the blood stem cells were found to lose their capacity to self-renew.
'We genetically knocked out netrin-1 in the stem cell niche of mouse bone marrow. The blood stem cells then lost their ability to self-renew. In contrast, when netrin-1 production was experimentally increased, they slept all the more deeply' said Dr Simon Renders, another lead author of the study. Therefore, the scientists concluded that neo-1 and netrin-1 are crucial to the lifelong self-renewal ability of blood stem cells in mice.
These findings are significant, as understanding the mechanisms behind all stem cell processes is key to developing new therapies that use them.