Chaotic dynamics for homeostatic hematopoiesis

Area of Science:

• Hematology
• Systems Biology
• Dynamical Systems Theory

Background:

• Homeostatic hematopoiesis is a complex dynamical process with significant cell quantity and proliferation rate variations.
• Extensive correlations and anti-correlations exist between different cell types within and between myeloid/lymphoid lineages.
• All blood cell types display synchronized, albeit rare, proliferation bursts across bone marrow, blood, and spleen.

Purpose of the Study:

• To investigate the dynamical features of hematopoiesis, including fluctuations, correlations, and chaotic behaviors.
• To develop a minimal mathematical model capturing these dynamics.
• To explain the transition from chaotic to oscillatory blood cell dynamics observed clinically, particularly in conditions like lymphoma.

Main Methods:

• Longitudinal study of blood cell counts in healthy mice.
• Analysis of leukocyte fluctuations for ergodicity and chaotic behavior.
• Development of a minimal mathematical model for hematopoiesis dynamics.
• Comparison of mouse cohorts with varying genetic backgrounds and ages.

Main Results:

• Leukocyte fluctuations in mice are ergodic and exhibit chaotic behavior with diverse timescales.
• A mathematical model successfully captured hematopoiesis dynamics (fluctuations, correlations, chaos).
• Simulations showed B-cell accumulation transitions dynamics from chaos to oscillations.
• Correlated blood cell fluctuations were observed across different mouse cohorts.

Conclusions:

• Hematopoiesis is a chaotic dynamical system with significant cell count variability.
• Mathematical modeling provides a framework for understanding hematopoiesis dynamics and disease transitions.
• B-cell accumulation can alter blood cell dynamics from chaos to oscillations, relevant to clinical observations.
• Correlated blood cell fluctuations are a fundamental aspect of hematopoiesis across diverse conditions.