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Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt
1CRC Department of Epithelial Cell Biology, Christie Hospital & Holt Radium Institute, Manchester, UK.
Development (Cambridge, England)
|December 1, 1990
Summary
Current stem cell definitions are problematic. This study proposes a new spiral model for adult stem cells, transit cells, and mature cells, viewing stemness as a capability spectrum rather than a fixed property.
Area of Science:
- Developmental Biology
- Cell Biology
- Tissue Engineering
Background:
- Current definitions of stem cells in adult mammalian tissues suffer from conceptual, semantic, and classification issues.
- Assessing stem cell function is challenging due to assay procedures potentially altering cell characteristics, akin to the uncertainty principle.
- Existing terminology for stem cell functions is often ill-defined, leading to confusion and conflicting experimental results.
Purpose of the Study:
- To address the limitations in current stem cell concepts by proposing a novel, experimentally amenable framework.
- To introduce a new model that reconciles opposing experimental findings by conceptualizing stemness as a spectrum of capabilities.
- To describe structured cell populations in tissues, including stem cells, transit cells, and mature cells.
Main Methods:
- Development of a novel conceptual framework based on the independence of proliferation and differentiation/maturation processes.
- Formulation of a spiral model to describe cell and tissue organization, illustrating the transition from stem cells to mature cells.
- Application of the model to the intestinal epithelium to analyze cell population dynamics.
Main Results:
- Proposed a model where stem cells divide without maturation, mature cells do not divide, and transit cells exhibit intermediate properties.
- The spiral model suggests stemness is a spectrum of capabilities, not a fixed property, reconciling diverse experimental outcomes.
- Analysis of intestinal crypts indicates 4-16 actual stem cells and 30-40 potential stem cells (clonogenic cells) in steady state.
Conclusions:
- The proposed spiral model offers a new perspective on stem cell organization and function in adult tissues.
- Transit cells can exhibit stem cell-like properties under specific conditions, highlighting the dynamic nature of stemness.
- Cell proliferation and differentiation are subject to regulatory controls influencing cellular trajectories within the spiral model.