The universal properties of stem cells as pinpointed by a simple discrete model

Zvia Agur, Yoaz Daniel, Yuval Ginosar

Research output: Contribution to journalArticlepeer-review

Abstract

The ability of a few stem-cells to repopulate a severely damaged bone marrow (BM) guarantees the stability of our physical existence, and facilitates successful BM transplantations. What are the basic properties of stern cells that enable the maintenance of the system's homeostasis? In the present work we attempt to answer this question by investigating a discrete (in time and phase-space) dynamical system. The model we present is shown to retrieve the essential properties of homeostasis, as reflected in BM functioning, namely, (a) to produce a constant amount of mature cells, and (b) to be capable of returning to this production after very large perturbations. The mechanism guaranteeing the fulfillment of these properties is extrinsic - negative feedback control in the micro-environment - and does not need additional stochastic assumptions. Nevertheless, the existence of a simple intrinsic control mechanism, a clock which determines the switch to differentiation, ascertains that the system does not admit non-trivial extinction states. This result may help clarifying some of the controversy about extrinsic versus intrinsic control over stem cell fate. It should be stressed that all conclusions are valid for any system containing progenitor and maturing cells.

Original languageEnglish
Pages (from-to)79-86
Number of pages8
JournalJournal of Mathematical Biology
Volume44
Issue number1
DOIs
StatePublished - Jan 2002
Externally publishedYes

Keywords

  • Bone marrow
  • Cellular automata
  • Hematopoiesis
  • Homeostasis
  • Negative feedback

ASJC Scopus subject areas

  • Applied Mathematics
  • Agricultural and Biological Sciences (miscellaneous)
  • Modeling and Simulation

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