The alpha(IIb)beta(3) integrin and GPIb-V-IX complex identify distinct stages in the maturation of CD34(+) cord blood cells to megakaryocytes
Autor: | A, Lepage, M, Leboeuf, J P, Cazenave, C, de la Salle, F, Lanza, G, Uzan |
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Rok vydání: | 2000 |
Předmět: |
Erythroid Precursor Cells
Cytoplasm Cell Membrane Permeability Microscopy Confocal Ploidies Time Factors Cell Membrane Infant Newborn Gene Expression Regulation Developmental Antigens CD34 Cell Differentiation Cell Separation Platelet Glycoprotein GPIIb-IIIa Complex Fetal Blood Flow Cytometry Antigens Differentiation Hematopoiesis Colony-Forming Units Assay Protein Transport Microscopy Fluorescence Platelet Glycoprotein GPIb-IX Complex Humans RNA Messenger Megakaryocytes Cells Cultured |
Zdroj: | Blood. 96(13) |
ISSN: | 0006-4971 |
Popis: | Megakaryocytopoiesis is a complex multistep process involving cell division, endoreplication, and maturation and resulting in the release of platelets into the blood circulation. Megakaryocytes (MK) progressively express lineage-restricted proteins, some of which play essential roles in platelet physiology. Glycoprotein (GP)Ib-V-IX (CD42) and GPIIb (CD41) are examples of MK-specific proteins having receptor properties essential for platelet adhesion and aggregation. This study defined the progressive expression of the GPIb-V-IX complex during in vitro MK maturation and compared it to that of GPIIb, an early MK marker. Human cord blood CD34(+) progenitor cells were cultured in the presence of cytokines inducing megakaryocytic differentiation. GPIb-V-IX expression appeared at day 3 of culture and was strictly dependent on MK cytokine induction, whereas GPIIb was already present in immature CD34(+) cells. Analysis by flow cytometry and of the messenger RNA level both showed that GPV appeared 1 day later than GPIb-IX. Microscopy studies confirmed the late appearance of GPV, which was principally localized in the cytoplasm when GPIb-IX was found on the cell surface, suggesting a delayed program of GPV synthesis and trafficking. Cell sorting studies revealed that the CD41(+)GPV(+) population contained 4N and 8N cells at day 7, and was less effective than CD41(+)GPV(-) cells in generating burst-forming units of erythrocytes or MK colonies. This study shows that the subunits of the GPIb-V-IX complex represent unique surface markers of MK maturation. The genes coding for GPIb-IX and GPV are useful tools to study megakaryocytopoiesis and for tissue-specific or conditional expression in mature MK and platelets. (Blood. 2000;96:4169-4177) |
Databáze: | OpenAIRE |
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