Transcriptional and epigenetic mechanisms of HSC subtype diversification

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The blood cells in the human body perform various tasks, including blood clotting, oxygen supply and diverse immune responses. A rare population of hematopoietic stem cells (HSCs) can produce all blood cells. During ageing, the ability of HSCs to generate blood cells significantly declines. They produce less red blood cells that transport oxygen and less immune cells that fight against infections, which are the potential causes of ageing-associate anaemia, immune deficiency and blood cancers. Yet, it is not clear how these changes of HSCs occur during ageing. In this project we aim to identify critical molecules that are controlling the blood cell production of HSCs. We have developed a technique that allows us to measure the blood cell production of a single HSC, and found that there are different types of HSCs with vastly different ability to make different types of blood cells. We now wish to examine if changes to the abundance of the different HSC subtypes can account for the declined production of red cells and immune cells in aged people. The aim of these studies is to identify key molecules that have influences on HSCs, and by targeting these molecules to prevent or ultimately revert the decline in blood cell production in aged people.