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| A ligand-receptor signaling threshold model of stem cell differentiation control: a biologically conserved mechanism applicable to hematopoiesis |
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| Author(s): Zandstra PW, Lauffenburger DA, Eaves CJ |
| Source: BLOOD Volume: 96 Issue: 4 Pages: 1215-1222 Published: AUG 15 2000 |
| Times Cited: 63 References: 119 |
| Abstract: A major limitation to the widespread use of hematopoietic stem cells (HSC) is the relatively crude level of our knowledge of how to maintain these cells in vitro without loss of the long-term multilineage growth and differentiation properties required for their clinical utility. An experimental and theoretical framework for predicting and controlling the outcome of HSC stimulation by exogenous cytokines would thus be useful, An emerging theme from recent HSC expansion studies is that a net gain in HSC numbers requires the maintenance of critical signaling ligand(s) above a threshold level. These ligand-receptor complex thresholds can be maintained, for example, by high concentrations of soluble cytokines or by extracellular matrix- or cell-bound cytokine presentation. According to such a model, when the relevant ligand-receptor interaction falls below a critical level, the probability of a differentiation response is increased; otherwise, self-renewal is favored. Thus, in addition to the identity of a particular receptor-ligand interaction being important to the regulation of stem cell responses, the quantitative nature of this interaction, as well as the dynamics of receptor expression, internalization, and signaling, may have a significant influence on stem cell fate decisions. This review uses examples from hematopoiesis and other tissue systems to examine existing evidence for a role of receptor activation thresholds in regulating hematopoietic stem cell self-renewal versus differentiation events. (Blood, 2000; 96:1215-1222) (C) 2000 by The American Society of Hematology. |
| Document Type: Review |
| Language: English |
| Reprint Address: Zandstra, PW (reprint author), Univ Toronto, Inst Biomat & Biomed Engn, Rm 407,Roseburgh Bldg,4 Taddle Creek Rd, Toronto, ON M5S 3G9 Canada |
Addresses:
1. Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON M5S 3G9 Canada
2. Univ Toronto, Dept Chem Engn & Appl Chem, Toronto, ON M5S 3G9 Canada
3. MIT, Ctr Biotechnol Proc Engn, Cambridge, MA 02139 USA
4. Univ British Columbia, British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1M9 Canada
5. Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 1M9 Canada |
| Publisher: AMER SOC HEMATOLOGY, 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA |
| Subject Category: Hematology |
| IDS Number: 358VQ |
| ISSN: 0006-4971 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |