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The marrow cell continuum: stochastic determinism.

P Quesenberry1, M Abedi, M Dooner

  • 1Department of Research, Roger Williams Medical Center, 825 Chalkstone Avenue, Providence, RI 02908, USA. pquesenberry@rwmc.org

Folia Histochemica Et Cytobiologica
|December 31, 2005
PubMed
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Hematopoiesis, the process of blood cell formation, is regulated by a continuum model, not a strict hierarchy. Stem cell phenotypes change reversibly with cell cycle transit, impacting differentiation.

Area of Science:

  • Hematology
  • Stem Cell Biology
  • Developmental Biology

Background:

  • Traditional models depict hematopoiesis as hierarchical.
  • Emerging data suggests a continuum model with deterministic and stochastic elements.
  • Primitive hematopoietic stem cells (HSCs) exhibit continuous or intermittent cycling.

Purpose of the Study:

  • To investigate the regulation of hematopoiesis beyond hierarchical models.
  • To explore the role of cell cycle transit in HSC phenotype and differentiation.
  • To present evidence supporting a continuum model of stem cell regulation.

Main Methods:

  • In vivo BrdU labeling to assess HSC cycling.
  • In vitro cytokine stimulation (IL-3, IL-6, IL-11, steel factor, thrombopoietin, FLT3 ligand) to induce synchronized cell cycle transit.

Related Experiment Videos

  • Analysis of HSC phenotypes including homing, engraftment, adhesion proteins, gene expression, and differentiation potential.
  • Assessment of non-hematopoietic differentiation (e.g., lung cells).

    • Main Results:

    • Primitive murine marrow cells (lin- Rdh(low) Hoe(low)) cycle continuously or intermittently.
    • Cytokine-induced cell cycle transit in HSCs is highly synchronized.
    • Cell cycle progression reversibly alters HSC homing, engraftment, adhesion proteins, gene expression, and hematopoietic differentiation.
    • Non-hematopoietic differentiation also demonstrates cycle-related, reversible modulation.

    Conclusions:

    • Hematopoiesis is regulated by a continuum model where stem cell phenotypes change dynamically.
    • Cell cycle transit alters chromatin structure, creating a changing landscape for transcriptional opportunities.
    • This continuum model explains reversible modulation of both hematopoietic and non-hematopoietic differentiation potential.