Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Hematopoietic stem cells (HSCs) are rare cells with a unique ability to give rise to all the cell types found in the human immune system, such as B cells, T cells, and monocytes. While rare, not all HSCs are the same, and when dysfunctional, HSCs can drive aggressive blood cancers such as acute myeloid leukemia (AML), with a 5-year net survival rate of only 23%. To predict who is at the highest risk of developing AML, there is a dire need to understand what HSC subtypes exist and which ones are more likely to turn cancerous. Sub-stratifying HSCs can help identify high-risk populations for AML and prioritize them for closer monitoring and clinical follow-up. However, HSCs are challenging to collect and are usually extracted via invasive bone marrow sampling, which requires a skilled practitioner to conduct. Without an accessible source of HSCs, tools to indirectly characterize HSC subtypes are sorely needed. This project tests whether the mature blood cells produced by HSCs could be harbingers of their parent HSCs. I hypothesize that particular gene signatures present in mature blood cells can accurately back-predict the same signatures in the HSCs that produced them, which would bypass the need to extract and analyze rare HSCs directly from bone marrow. I will analyze mature blood cells collected from 397 participants in the Ontario Health Study through non-invasive blood sampling and capture which genes are expressed by each individual cell, using single-cell RNA sequencing technology. I will identify shared gene signatures between mature blood cells and HSCs and computationally trace signatures directly from HSCs to mature cells. This project will be the first to comprehensively link mature blood cell signatures with HSC subtypes using large-scale human cohort data, and may inform the development of a risk prediction tool to help clinicians understand which patients are most vulnerable to AML development using accessible blood-based tests.