4.5 Article

A STRUCTURED POPULATION MODEL OF CELL DIFFERENTIATION

Journal

SIAM JOURNAL ON APPLIED MATHEMATICS
Volume 71, Issue 6, Pages 1918-1940

Publisher

SIAM PUBLICATIONS
DOI: 10.1137/100816584

Keywords

structured population dynamics; transport equation; stem cells; cell differentiation; stability analysis

Funding

  1. CNPq-INRIA INVEBIO
  2. ERC of German Research Council (DFG)
  3. WIN Kolleg of Heidelberg Academy of Sciences and Humanities
  4. Collaborative Research Center [SFB 873]
  5. CNPq [302161/2003-1, 474085/2003-1]

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We introduce and analyze several aspects of a new model for cell differentiation. It assumes that differentiation of progenitor cells is a continuous process. From the mathematical point of view, it is based on partial differential equations of transport type. Specifically, it consists of a structured population equation with a nonlinear feedback loop. This models the signaling process due to cytokines, which regulate the differentiation and proliferation process. We compare the continuous model to its discrete counterpart, a multicompartmental model of a discrete collection of cell subpopulations recently proposed by Marciniak-Czochra et al. [Stem Cells Dev., 18 (2009), pp. 377-386] to investigate the dynamics of the hematopoietic system. We obtain uniform bounds for the solutions, characterize steady state solutions, and analyze their linearized stability. We show how persistence or extinction might occur according to values of parameters that characterize the stem cells' self-renewal. We also perform numerical simulations and discuss the qualitative behavior of the continuous model vis a vis the discrete one.

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