Speaker
Description
Blood cell formation is maintained throughout the lifespan of an organism by a small population of hematopoietic (blood-forming) stem cells (HSCs). HSCs sustain their population through self-renewal while simultaneously giving rise to more differentiated offspring, referred to as progenitors and precursors, that mature into the various blood cell types. Over time, HSCs accumulate mutations that can confer growth advantages and trigger clonal expansion. This leads to a condition known as clonal hematopoiesis of indeterminate potential (CHIP). The incidence of clonal hematopoiesis increases with age, however, the underlying mechanisms are not fully understood. As CHIP can eventually transform into severe blood cancers, it is crucial to understand and quantitatively predict its dynamics. Evidence suggests that the interplay between mutation accumulation and age-related systemic changes, such as chronic inflammation, altered growth factor levels, and changes in the bone marrow micro-environment, contributes to CHIP evolution. We propose mechanistic mathematical models that account for stem and progenitor cell self-renewal and differentiation, nonlinear feedback regulation, chronic inflammation, and changes in the stem cell niche to understand how these processes influence clonal dynamics. The models are informed by data on steady-state blood cell formation and clonal expansion after stem cell transplantation.
