title: Interrelation between polyploidization and megakaryocyte differentiation: a gene profiling approach.
abstract: Polyploidization is a part of the normal developmental process leading to platelet production during megakaryocyte (MK) differentiation. Ploidization is mainly involved in cell enlargement, but it is not clear whether gene expression is modified during MK ploidization. In this study, human MKs were grown from CD34(+) cells in the presence of thrombopoietin and sorted according to their ploidy level. A pangenomic microarray technique was applied to compare gene expression in 2N-, 4N-, 8N-, and 16N-sorted MKs. Using hierarchical clustering, we demonstrated that 2N and 4N MKs or 8N and 16N MKs are 2 different close populations with 105 discriminating genes. In the second approach, we determined the profile of genes that were continuously down- and up-regulated during polyploidization. Among the 100 down-regulated genes, 24 corresponded to genes involved in DNA replication and repair. The great majority of up-regulated genes corresponded to genes directly involved in platelet functions, such as genes encoding specific platelet glycoproteins and alpha-granule proteins, actin and microtubule cytoskeleton, factors involved in signaling, and transport proteins. Together, these results suggest that MK polyploidization per se does not regulate gene expression but is intrinsically included in the differentiation process.
authors.affiliation: INSERM Unité 790, Institut Gustave Roussy, 1 rue Camille Desmoulins, 94805 Villejuif, France. hraslova@igr.fr
authors.forename: Hana
authors.initials: H
authors.lastname: Raslova
authors.forename: Audrey
authors.initials: A
authors.lastname: Kauffmann
authors.forename: Dalila
authors.initials: D
authors.lastname: Sekkaï
authors.forename: Hugues
authors.initials: H
authors.lastname: Ripoche
authors.forename: Fréderic
authors.initials: F
authors.lastname: Larbret
authors.forename: Thomas
authors.initials: T
authors.lastname: Robert
authors.forename: Diana
authors.initials: D
authors.lastname: Tronik Le Roux
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.forename: Najet
authors.initials: N
authors.lastname: Debili
authors.forename: Philippe
authors.initials: P
authors.lastname: Dessen
authors.forename: Vladimir
authors.initials: V
authors.lastname: Lazar
authors.forename: William
authors.initials: W
authors.lastname: Vainchenker
mesh_terms: D018952:Antigens, CD34; D001792:Blood Platelets; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D011003:Ploidies; D013926:Thrombopoietin / Q000494:pharmacology
chemical_list: D018952:Antigens, CD34; D013926:Thrombopoietin