PA03_03 - What does your blood remember - the memory of hematopoietic stem cells.
PA03_03
What does your blood remember - the memory of hematopoietic stem cells.
K. Szade1,* on behalf of Laboratory of Stem Cell Biology, Jagiellonian University
1Laboratory of Stem Cell Biology, Jagiellonian University, Krakow, Poland
Abstract: Hematopoietic stem cells (HSCs) sustain lifelong blood production by continuously generating all mature blood cell types. This process requires tight regulation to ensure that the composition of blood adapts dynamically to physiological demands, including rapid responses to stressors such as infection or injury. While this system is remarkably robust, HSCs themselves are long-lived and therefore accumulate the effects of aging and environmental challenges over time.
Here, we demonstrate that HSCs acquire a form of functional “memory” that influences how they maintain and regenerate the hematopoietic system. During aging, HSCs exhibit a well-known bias toward myeloid and platelet production. Using a mouse model, we show that this shift arises from both changes in clonal composition and progressive epigenetic drift. Importantly, we identify phenotypic markers that allow prospective isolation of HSCs predisposed to myeloid bias.
We further investigate how acute hematopoietic stress impacts HSC function. Although HSCs appear to recover after stress and return to baseline function, we find that prior stimulation leaves a lasting imprint. Upon secondary challenge, these cells respond differently, revealing a latent memory of the initial insult that alters their functional output.
Finally, we examine how pathological stress affects HSCs in the context of acute lymphoblastic leukemia. We uncover aberrant HSC phenotypes and disrupted cellular interactions driven by expanding leukemic blasts, highlighting how disease environments reshape stem cell behavior.
Together, our findings indicate that HSCs integrate lifelong experiences into a functional memory that influences their behavior. This memory shapes blood production in aging, stress, and disease, providing new insight into how stem cell history impacts hematopoietic health and dysfunction.
Disclosure of Interest: None declared