Delta-4 Notch ligand promotes erythroid differentiation of human umbilical cord blood CD34+ cells
| Autor: | Mayuko Yamamoto, Ryuichi Motoda, Kunzo Orita, Akira Sugimoto, Shuji Nakamura, Toshiya Inoue, Fumiyuki Yamasaki, Motoyuki Suzuki |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Stromal cell medicine.medical_treatment CD34 Notch signaling pathway Gene Expression Antigens CD34 Stem cell factor Transfection Cell Line Mice Genetics medicine Animals Humans Glycophorin Erythropoiesis Serrate-Jagged Proteins Glycophorins Molecular Biology Erythroid Precursor Cells biology Calcium-Binding Proteins Intracellular Signaling Peptides and Proteins Membrane Proteins Cell Differentiation Cell Biology Hematology Fetal Blood Molecular biology Recombinant Proteins Haematopoiesis Cytokine Erythropoietin biology.protein Intercellular Signaling Peptides and Proteins Female Jagged-2 Protein Stromal Cells Jagged-1 Protein Signal Transduction medicine.drug |
| Zdroj: | Experimental Hematology. 34:424-432 |
| ISSN: | 0301-472X |
| Popis: | Objective Important roles of Notch signaling have been demonstrated in hematopoiesis. In many cases, activation of the Notch pathway leads to the inhibition of differentiation of immature precursors, suggesting a potential role in self-renewal promotion. However, the function of Notch and Notch ligands is not so straightforward because it is considerably dependent on cytokine context. In this study, we analyzed effects of one Notch ligand, Delta-4, whose function is less clear than others, such as Delta-1 and Jagged-1 and -2. Methods CD34 + cells isolated from human umbilical cord blood were cocultured with a Delta-4-expressing murine stromal cell line, SC9-19, and induced to erythroid differentiation by adding stem cell factor and erythropoietin. To examine the involvement of Delta-4, we utilized stromal cell subclones expressing Delta-4 protein at higher or lower level than parental SC9-19 by plasmid transfection. Erythroid maturation was examined by surface phenotype (CD34 and glycophorin A) and cytospin morphology. Recombinant human Delta-4 protein was prepared to analyze direct effects of Delta-4. Results Under erythroid lineage-inducing conditions, we found that the increase in Delta-4 expression of SC9-19 promoted erythroid differentiation whereas the decrease in Delta-4 expression inhibited it. Morphologic examination as well as colony formation analysis supported this observation. Moreover, the experiment using recombinant Delta-4 provided direct evidence of the Delta-4 activity found in coculture system. Conclusions By modifying Delta-4 expression of the stromal cells and using the recombinant protein, we demonstrated that Delta-4 had a differentiation promoting activity for human primitive hematopoietic cells into erythroid lineage. |
| Databáze: | OpenAIRE |
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