Control of hematopoietic stem/progenitor cell fate by transforming growth factor-beta
| Autor: | Jacques Hatzfeld, Nicolas O. Fortunel, Marie-Noëlle Monier, Antoinette Hatzfeld |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Cancer Research
Cellular differentiation Cell Culture Techniques Down-Regulation Stem cell factor Antigens CD34 Cell Separation Biology Monocytes Cell Line Transforming Growth Factor beta Proto-Oncogene Proteins Humans Progenitor cell Receptors Cytokine Cell potency Induced stem cells Cell Cycle Receptor Protein-Tyrosine Kinases General Medicine Fetal Blood Hematopoietic Stem Cells Receptors Interleukin-6 Cell biology Clone Cells Neoplasm Proteins Endothelial stem cell Oncology Immunology Stem cell Receptors Thrombopoietin Adult stem cell |
| Zdroj: | Oncology research. 13(6-10) |
| ISSN: | 0965-0407 |
| Popis: | A major obstacle to the use of adult somatic stem cells for cell therapy is our current inability to fully exploit stem cell self-renewal properties. The challenge is to obtain defined culture systems where cycling of primitive stem/progenitor cells is stimulated, while their differentiation and senescence are prevented. The cytokine transforming growth factor-beta1 (TGF-beta1) appears as a potential regulator of hematopoietic stem/ progenitor cell self-renewal, as it participates in the control of cell proliferation, survival/apoptosis, and cell immaturity/differentiation. TGF-beta1 acts via a complex regulatory network involving intracellular signaling molecules and cell surface receptors. According to the High Proliferative Potential-Quiescent (HPP-Q) cell working model that we introduced previously, TGF-beta1 maintains primitive hematopoietic stem/progenitor cells in a quiescent or slow cycling state, in part by downmodulating the cell surface expression of mitogenic cytokine receptors, thus preventing cells from responding rapidly to a mitogenic signal. We have established that this modulation concerns the tyrosine kinase receptors KIT and FLT3, and the IL-6 receptor (IL-6R), three important cytokine receptors controlling early human hematopoietic stem/progenitor cell development. In this article. we show a similar modulation by TGF-beta1 of a fourth receptor: the TPO receptor (MPL). As a consequence, TGF-beta1 decreased the cell cycle entry of stem/progenitor cells stimulated by the respective ligands of these receptors, the cytokines SF, FL, IL-6, and TPO, whereas neutralization of TGF-beta1 increased the cell responsiveness to these mitogenic cytokines. Other aspects of the function of TGF-beta1 in the regulation of early hematopoiesis (i.e., the control of stem/progenitor cell survival and immaturity) are reviewed in the discussion. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|