Dissecting the role of Neogenin-1, a novel receptor required for hematopoietic stem cell proliferation and engraftment (LSBR 1703)
Project leader: Prof. Dr. Gerald de Haan, University Medical Center Groningen
PhD student: Arthur Flohr Svendsen (April 2018 – March 2022)
Medical conditions like anemia, deficient immune system and different kinds of leukemia happen more often in elderly people. It was later found that different kinds of damage, which happen in these stem cells, are actually partially responsible for these diseases. Over the past decades we have started to understand the different causes for this aging effect, ranging from DNA damage in these stem cells, to alterations in different cells that surround stem cells in the bone marrow. Understanding what causes stem cell to age would allow new therapies strategies which can mitigate such medical conditions.
In this context, we uncovered that Neogenin-1 is activated only in stem cells and gets rapidly deactivated when these cells differentiate into mature blood cells. We also confirmed that old stem cells have more activated Neo1, thus making Neo1 a good marker for old stem cells. Neo1 is localized in the membrane of stem cells and can communicate different signals from outside to the inside of the cell. Through further experiments we established that Neo1 is part of a mechanism that stem cells use to sense and later attachment to specific places in the bone marrow.