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Related Experiment Videos

Intrinsic hematopoietic stem cell/progenitor plasticity: Inversions.

Gerald A Colvin1, Jean-François Lambert, Brian E Moore

  • 1Roger Williams Medical Center, Department of Research, Adele Decof Cancer Center, Providence, Rhode Island 02908-4735, USA. gcolvin@rwmc.org

Journal of Cellular Physiology
|February 24, 2004
PubMed
Summary

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Murine engraftable stem cells (ESCs) and progenitors exist in a reversible continuum, not a hierarchy. These primitive marrow cells reversibly shift between states without differentiation, forming a fluctuating continuum.

Area of Science:

  • Hematopoiesis
  • Stem Cell Biology
  • Cell Cycle Regulation

Background:

  • Traditional models propose a hierarchical system where stem cells differentiate into progenitors.
  • The dynamic relationship between stem cells and progenitors requires further investigation.

Purpose of the Study:

  • To investigate the relationship between murine engraftable stem cells (ESCs) and progenitors in vitro.
  • To determine if the stem cell-progenitor relationship is hierarchical or a continuum.

Main Methods:

  • Serial culture of murine marrow cells (B6.SJL and BALB/c) with thrombopoietin (TPO), FLT-3 ligand (FLT-3L), and steel factor.
  • Assessment of progenitor capacity (HPP-CFC, CFU-c) and ESC capacity.
  • Determination of cell cycle status of purified stem cells using tritiated thymidine incorporation and cell counts.

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Main Results:

  • An inverse and reversible relationship was observed between ESCs and progenitors during the first cell cycle transit.
  • Progenitor/stem cell inversions occurred consistently at 28-32 hours of culture, correlating with early S-phase.
  • Significant reversible increases in progenitor numbers were accompanied by decreases in ESC numbers.

Conclusions:

  • Murine primitive marrow cells exist as a reversible continuum, not a strict hierarchy.
  • Stem cells and progenitors can reversibly shift between states without undergoing differentiation.
  • These findings challenge traditional stem cell models and highlight a dynamic, fluctuating continuum.