A Matter of Timing: A Genome-Wide Investigation of Hematopoietic Stem Cell Aging

Medical conditions like anemia, deficient immune system and different kinds of leukemia happen more often in elderly people. The cause of these conditions can linked to changes happening in the source which generates all these cells, the so-called blood stem cells. Over the past decades we have started to understand the different causes for this aging effect, but it is not yet completely understood.In this PhD thesis we aim to provide new insights into the molecular changes which happen during life which can explain these medical conditions and the overall decline in stem cell function. Specifically, we had a close look into different phenomena around transcription, the process of making RNA from DNA. Performing an in-depth analyses we discovered that aged stem cells produce more RNA. There is an enrichment for RNAs coding for specific proteins, responsible for communication between inside and outside of these cells, further suggesting changes in the cross-talk between stem cells and their environment. Next, we found that there is a loss of epigenetic regulation (the molecular layer that regulates RNA transcription) in these aged stem cells. These cells control transcription more loosely, which can explain why there is a decline in function. Lastly, we focused on gene uncovered from this analysis which had an unknown function in the blood system. We then describe its importance for stem cell identify.Taken together, this thesis aimed to identify molecular targets that can be pharmacologically modulated in order to promote prolonged healthy aging