Mobilization and homogeneity of healthy hematopoietic stem cells during hematological malignancy 3191

Abstract Description Hematopoietic stem cells (HSCs) are multipotent and capable of self-renewal, producing all immune cells. HSCs are heterogeneous, showing differences in blood lineage production and responses to stress, such as transient proliferation and migration. Inflammation can disrupt HSC function, but the mechanisms remain unclear; so understanding how inflammation affects HSCs could reveal important aspects of their diversity and behavior. We examined how acute sterile inflammation impacts the HSC biology using a pre-clinical mouse model of acute myeloid leukemia (AML) paired with flow cytometric analysis. Our results showed a rapid decline in marrow-resident HSCs after disease onset, with a corresponding expansion of phenotypically distinct splenic HSCs. These egressed HSCs shared surface markers with those lost from the marrow, suggesting a subset of HSCs that are particularly sensitive to inflammation and mobilization. As disease progressed, remaining marrow HSCs became more quiescent. Interestingly, transcriptomic analysis revealed that these residual HSCs were primed for balanced lineage output and showed increased TGFβ signaling, suggesting that a quiescent, non-biased HSC population has a selective advantage under inflammatory stress. These findings may provide insights into how inflammation compromises HSC function, offering potential explanations for impaired hematopoietic recovery following inflammatory insults and guiding future therapeutic strategies. Funding Sources 1T32GM146611-01A1, Mark Foundation Endeavor Topic Categories Hematopoiesis and Immune System Development (HEM)