open access

Vol 43, No 4 (2005)
Original paper
Published online: 2005-12-31
Submitted: 2011-12-19
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The marrow cell continuum: stochastic determinism.

P Quesenberry, M Abedi, M Dooner, G Colvin, F Martin Sanchez-Guijo, J Aliotta, J Pimentel, G Dooner, D Greer, D Demers, P Keaney, A Peterson, L Luo, B Foster
Folia Histochem Cytobiol 2005;43(4):187-190.

open access

Vol 43, No 4 (2005)
ORIGINAL PAPERS
Published online: 2005-12-31
Submitted: 2011-12-19

Abstract

Traditional models of hematopoiesis have been hierarchical in nature. Over the past 10 years, we have developed data indicating that hematopoiesis is regulated in a continuum with deterministic and stochastic components. We have shown that the most primitive stem cells, as represented by lineage negative rhodamine(low) Hoechst(low) murine marrow cells are continuously or intermittently cycling as determined by in vivo BrdU labeling. When marrow stem cells are induced to transit cell cycle by in vitro exposure to cytokines, either IL-3, IL-6, IL-11, and steel factor or thrombopoietin, FLT3 ligand, and steel factor, they progress through cycle in a highly synchronized fashion. We have determined that when the stem cells progress through a cytokine stimulated cell cycle the homing, engraftment, adhesion protein, global gene expression, and hematopoietic differentiation phenotypes all change in a reversible fashion. This has led to the continuum model, in which, with cycle transit, chromatin is continually changing altering open transcription areas and providing a continually changing landscape of transcriptional opportunity. More recently, we have extended the changing differentiation profiles to differentiation into lung cells and found that non-hematopoietic differentiation also shows cycle related reversibly modulation. These observations all together support a continuum model of stem cell regulation in which the phenotype of the marrow stem cells is continually and reversibly changing over time.

Abstract

Traditional models of hematopoiesis have been hierarchical in nature. Over the past 10 years, we have developed data indicating that hematopoiesis is regulated in a continuum with deterministic and stochastic components. We have shown that the most primitive stem cells, as represented by lineage negative rhodamine(low) Hoechst(low) murine marrow cells are continuously or intermittently cycling as determined by in vivo BrdU labeling. When marrow stem cells are induced to transit cell cycle by in vitro exposure to cytokines, either IL-3, IL-6, IL-11, and steel factor or thrombopoietin, FLT3 ligand, and steel factor, they progress through cycle in a highly synchronized fashion. We have determined that when the stem cells progress through a cytokine stimulated cell cycle the homing, engraftment, adhesion protein, global gene expression, and hematopoietic differentiation phenotypes all change in a reversible fashion. This has led to the continuum model, in which, with cycle transit, chromatin is continually changing altering open transcription areas and providing a continually changing landscape of transcriptional opportunity. More recently, we have extended the changing differentiation profiles to differentiation into lung cells and found that non-hematopoietic differentiation also shows cycle related reversibly modulation. These observations all together support a continuum model of stem cell regulation in which the phenotype of the marrow stem cells is continually and reversibly changing over time.
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About this article
Title

The marrow cell continuum: stochastic determinism.

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 43, No 4 (2005)

Article type

Original paper

Pages

187-190

Published online

2005-12-31

Bibliographic record

Folia Histochem Cytobiol 2005;43(4):187-190.

Authors

P Quesenberry
M Abedi
M Dooner
G Colvin
F Martin Sanchez-Guijo
J Aliotta
J Pimentel
G Dooner
D Greer
D Demers
P Keaney
A Peterson
L Luo
B Foster

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