Grant: Operating Grant

All the different types of cells present in the blood originate from a common progenitor cell called hematopoietic stem cells (HSCs). HSCs can differentiate into various cell types specialized in performing different functions. For instance, red blood cells are used to transport oxygen molecules from the lungs to the various organs, whereas a series of white blood cells play various roles in innate and adaptive immunity. Understanding the differentiation process that allows HSCs to produce various blood cell types is critical since cancers such as leukemia and lymphomas can arise if this process is perturbed. In cells, the genetic material (DNA) is associated with various proteins. While all cells from an individual carry essentially the same DNA, these cells have very different characteristics and functions. What makes the different cells in our body mostly lies within the way DNA is packaged with proteins. This "packaging" is heritable just like the sequence of DNA itself. Interestingly, while mutations in cancer cells cannot be repaired by therapeutic interventions, some drugs can modify DNA packaging. Therefore, researchers are developing drugs to treat cancer by modifying DNA packaging in cancer cells. In that context, it becomes of high importance to study DNA packaging in key cells like HSCs and their derivatives. The objective of this proposal is to characterize the way that DNA is packaged in HSCs and, more importantly, to determine how this packaging changes as HSCs differentiate into the various blood cell types. This will inform us about how HSCs can give rise to all kinds of blood cells, will constitute a framework to understand how leukemia and lymphoma arise, and will provide important clues about how to cure these diseases.