Hematopoietic stem cells (HSCs) are the adult stem cells in the bone marrow that are responsible for the replenishment of all blood cells. For example, red and white blood cells. When these cells age, they will start functioning less well and causes the chance of blood diseases such as blood cancer to increase. Different processes and components inside the cell can influence the behavior of HSCs. One of these components are microRNAs. These small pieces of genetic material can influence the production of proteins in the cell. It was previously discovered that microRNA-125a can improve the function of HSCs. When the abundance of microRNA-125a is increased the cells grow faster and produce more progeny. In this thesis we study how microRNA-125a can have its effects on stem cells. First, we discuss the role of microRNAs in the aging process of HSCs. Then we study if the effects of microRNA-125a on HSCs are reversible in murine cells. We also study which proteins are affected by microRNA-125a and how the microRNA binds to its targets. Additionally, we investigate if the observed effects are also true for human HSCs, which seems to be the case. In the final chapter we discuss how micorRNA-125a might be used for clinical purposes. In the future it might be possible to utilize microRNA-125a or its mechanism to expand HSCs. This is something that is not possible to date and could be of great importance for bone marrow transplants.
|Kwalificatie||Doctor of Philosophy|
|Datum van toekenning||11-okt-2021|
|Plaats van publicatie||[Groningen]|
|Status||Published - 2021|