title: Stromal cell-derived factor 1alpha increases polyploidization of megakaryocytes generated by human hematopoietic progenitor cells.
abstract: The alpha chemokine receptor CXCR4 has been shown to be expressed on human hematopoietic progenitor cells and during the megakaryocytic differentiation pathway. Stromal cell-derived factor 1 (SDF-1) is the ligand for CXCR4. In this study, the role of SDF-1alpha in megakaryocytopoiesis was investigated. CD34(+) progenitors purified from peripheral blood were grown in serum-free liquid suspension culture supplemented with thrombopoietin to obtain a virtually pure megakaryocytic progeny. In this condition, the addition of SDF-1alpha gives rise to megakaryocytes (MKs) showing an increased DNA content and a rise of lobated nuclei, as compared with untreated cells: at day 5, approximately 20% of the cells already showed the presence of more than one nuclear lobe versus fewer than 5% in the control cells; at day 12, approximately 85% of the cells were of large size and markedly polyploid, whereas approximately 60% of the control cells were polyploid, showed fewer lobes, and were a smaller size. This effect was dose-dependent and did not affect the megakaryocytic proliferation. Experiments with the mitogen-activated protein kinase (MAPK) inhibitor PD98059 suggested a role for MAPK pathway on SDF-1alpha-induced endomitosis. Furthermore, SDF-1alpha induced a significant increase in the number of proplatelet-bearing MKs and promoted the migration of megakaryocytic cells. Treatment with SDF-1alpha caused reduction in CXCR4 abundance on the plasma membrane, seemingly owing to receptor internalization. Furthermore, the presence of SDF-1alpha did not affect the expression of megakaryocytic markers, indicating that differentiation and polyploidization are independently regulated events.
authors: Department of Clinical Biochemistry and the Department of Hematology-Oncology, Istituto Superiore di Sanità, Rome, Italy.
authors: R
authors: R
authors: Guerriero
authors: G
authors: G
authors: Mattia
authors: U
authors: U
authors: Testa
authors: C
authors: C
authors: Chelucci
authors: G
authors: G
authors: Macioce
authors: I
authors: I
authors: Casella
authors: P
authors: P
authors: Samoggia
authors: C
authors: C
authors: Peschle
authors: H J
authors: HJ
authors: Hassan
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology*; D011003:Ploidies
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC