Exploring how diabetes causes increased proliferation of haematopoietic stem cells carrying a mutation in DNMT3A

Summary Clonal haematopoiesis of indeterminant potential (CHIP), caused by somatic mutations in haematopoietic stem cells (HSCs) causes a growth advantage in these cells causing them to outcompete non-mutated HSCs. CHIP was commonly thought to be a prerequisite to leukaemia, the disease ultimately responsible for death in these individuals. However, it was recently shown that people with CHIP more frequently die of cardiovascular disease. Interestingly, there is an association with CHIP and diabetes, but this has not been explored experimentally. We discovered that diabetes enhances the proliferation of HSCs carrying the most common mutation in CHIP (DNMT3A). This project will explore mechanism behind this using a variety of unique animal models and experimental techniques. This project will give the student a valuable insight into stem cell biology within a highly successful world class research laboratory.

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