Multistage feedback-driven compartmental dynamics of hematopoiesis
Nathaniel Vincent Mon Père,
Tom Lenaerts,
Jorge Manuel dos Santos Pacheco,
David Dingli
Affiliations
Nathaniel Vincent Mon Père
Interuniversity Institute of Bioinformatics in Brussels, Université libre de Bruxelles – Vrije Universiteit Brussel, 1050 Brussels, Belgium; Applied Physics group, Department of Physics, Vrije Universiteit Brussel, 1050 Brussels, Belgium; Machine Learning Group, Département d'Informatique, Université libre de Bruxelles, 1050 Brussels, Belgium
Tom Lenaerts
Interuniversity Institute of Bioinformatics in Brussels, Université libre de Bruxelles – Vrije Universiteit Brussel, 1050 Brussels, Belgium; Machine Learning Group, Département d'Informatique, Université libre de Bruxelles, 1050 Brussels, Belgium; AI lab, Computer Science Department, Vrije Universiteit Brussel, 1050 Brussels, Belgium
Jorge Manuel dos Santos Pacheco
Centro de Biologia Molecular e Ambiental, Universidade do Minho, 4710–057 Braga, Portugal; Departamento de Matemática e Aplicações, Universidade do Minho, 4710–057 Braga, Portugal; ATP-group, P-2744-016 Porto Salvo, Portugal
David Dingli
Division of Hematology and Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA; Corresponding author
Summary: Human hematopoiesis is surprisingly resilient to disruptions, providing suitable responses to severe bleeding, long-lasting immune activation, and even bone marrow transplants. Still, many blood disorders exist which push the system past its natural plasticity, resulting in abnormalities in the circulating blood. While proper treatment of such diseases can benefit from understanding the underlying cell dynamics, these are non-trivial to predict due to the hematopoietic system's hierarchical nature and complex feedback networks. To characterize the dynamics following different types of perturbations, we investigate a model representing hematopoiesis as a sequence of compartments covering all maturation stages—from stem to mature cells—where feedback regulates cell production to ongoing necessities. We find that a stable response to perturbations requires the simultaneous adaptation of cell differentiation and self-renewal rates, and show that under conditions of continuous disruption—as found in chronic hemolytic states—compartment cell numbers evolve to novel stable states.
