Chaotic dynamics for homeostatic hematopoiesis

Homeostatic hematopoiesis is a dynamical process, characterized by large variations (e.g., with coefficients of variation larger than 1) of cell quantities, cell proliferation rates, and extensive correlations/anticorrelations between cell types within the myeloid/lymphoid lineage, and between lineages. All cell types exhibit rare but synchronized bursts of proliferation in the bone marrow, blood and spleen. Through longitudinal study of the blood contents of healthy mice, we found that leukocyte fluctuations are ergodic yet subject to chaotic behaviors characterized by a broad spectrum of characteristic timescales. We then built a minimal mathematical model to capture these dynamical features of hematopoiesis (fluctuations, correlations, and chaos) and explain how the accumulation of B cells (e.g. during lymphoma development) would transition the blood cell dynamics from chaos to oscillations as observed clinically. Finally, we demonstrated the ubiquity of the correlated blood cell fluctuations by comparing mouse cohorts of different genetic backgrounds and ages.