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12:03
Phenotypic Analysis and Isolation of Murine Hematopoietic Stem Cells and Lineage-committed Progenitors
Published on: July 8, 2012
The stem cell continuum: a new model of stem cell regulation
G A Colvin1, P J Quesenberry, M S Dooner
1Research Department, Roger Williams Medical Center, 825 Chalkstone Avenue, Providence RI, 02908, USA. pquesenberry@rwmc.org
Handbook of Experimental Pharmacology
|December 24, 2005
Summary
Hematopoiesis, the process of blood cell formation, may be a continuum rather than hierarchical. Stem cell function and differentiation potential change reversibly with cell cycle passage, suggesting population-based study and mathematical modeling.
Area of Science:
- Hematology
- Stem Cell Biology
- Cell Cycle Regulation
Background:
- Traditional models of hematopoiesis are predominantly hierarchical.
- Recent research suggests a continuum of transcriptional states at the stem/progenitor level.
- Hematopoietic stem cells (HSCs) exhibit dynamic behavior, cycling slowly or intermittently.
Purpose of the Study:
- To investigate the role of cell cycle dynamics in hematopoietic stem cell function.
- To explore the plasticity of HSCs and their differentiation potential in response to cell cycle transit.
- To challenge the discrete entity model of HSCs and advocate for population-based studies.
Main Methods:
- Analysis of global gene expression in HSCs at different cell cycle phases.
- Assessment of functional phenotypes, including engraftment, adhesion, and cytokine receptor expression, correlated with cell cycle.
- Evaluation of marrow differentiation potential during cell cycle transit.
- Investigation of murine marrow stem cell homing and differentiation into pulmonary cells.
Main Results:
- Cell cycle passage induces reversible alterations in HSC functional phenotypes.
- Global gene expression patterns are significantly altered with cell cycle progression.
- The differentiation potential of marrow stem cells varies markedly with cell cycle.
- Murine marrow stem cells demonstrate plasticity, including lung homing and pulmonary cell conversion.
Conclusions:
- Hematopoiesis may represent a continuum of transcriptional opportunity, not discrete hierarchical steps.
- Bone marrow stem cells are best studied as populations due to their cycle-related plasticity.
- Mathematical modeling is increasingly crucial for understanding dynamic stem cell behavior.
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