title: Dux4 controls migration of mesenchymal stem cells through the Cxcr4-Sdf1 axis.
abstract: We performed transcriptome profiling of human immortalized myoblasts (MB) transiently expressing double homeobox transcription factor 4 (DUX4) and double homeobox transcription factor 4 centromeric (DUX4c) and identified 114 and 70 genes differentially expressed in DUX4- and DUX4c-transfected myoblasts, respectively. A significant number of differentially expressed genes were involved in inflammation, cellular migration and chemotaxis suggesting a role for DUX4 and DUX4c in these processes. DUX4 but not DUX4c overexpression resulted in upregulation of the CXCR4 (C-X-C motif Receptor 4) and CXCL12 (C-X-C motif ligand 12 also known as SDF1) expression in human immortalized myoblasts. In a Transwell cell migration assay, human bone marrow-derived mesenchymal stem cells (BMSCs) were migrating more efficiently towards human immortalized myoblasts overexpressing DUX4 as compared to controls; the migration efficiency of DUX4-transfected BMSCs was also increased. DUX4c overexpression in myoblasts or in BMSCs had no impact on the rate of BMSC migration. Antibodies against SDF1 and CXCR4 blocked the positive effect of DUX4 overexpression on BMSC migration. We propose that DUX4 controls the cellular migration of mesenchymal stem cells through the CXCR4 receptor.
authors.affiliation: UMR 8126, Univ. Paris-Sud, CNRS, Institut de Cancérologie Gustave-Roussy, Villejuif, France.|LIA1066 Laboratoire Franco-Russe de Recherches en Oncologie, Villejuif, France.
authors.forename: Petr
authors.initials: P
authors.lastname: Dmitriev
authors.affiliation: LIA1066 Laboratoire Franco-Russe de Recherches en Oncologie, Villejuif, France.|N.K. Koltzov Institute of Developmental Biology, RAS, Moscow, Russia.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Kiseleva
authors.affiliation: LIA1066 Laboratoire Franco-Russe de Recherches en Oncologie, Villejuif, France.|N.K. Koltzov Institute of Developmental Biology, RAS, Moscow, Russia.
authors.forename: Olga
authors.initials: O
authors.lastname: Kharchenko
authors.affiliation: LIA1066 Laboratoire Franco-Russe de Recherches en Oncologie, Villejuif, France.|N.K. Koltzov Institute of Developmental Biology, RAS, Moscow, Russia.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Ivashkin
authors.affiliation: LIA1066 Laboratoire Franco-Russe de Recherches en Oncologie, Villejuif, France.|N.K. Koltzov Institute of Developmental Biology, RAS, Moscow, Russia.|Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia.
authors.forename: Andrei
authors.initials: A
authors.lastname: Pichugin
authors.affiliation: Functional Genomics Unit, Institut de Cancérologie Gustave-Roussy, Villejuif, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Dessen
authors.affiliation: Functional Genomics Unit, Institut de Cancérologie Gustave-Roussy, Villejuif, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Robert
authors.affiliation: Laboratory of Molecular Biology, Research Institute for Health Sciences and Technology, University of Mons, Mons, Belgium.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Coppée
authors.affiliation: Laboratory of Molecular Biology, Research Institute for Health Sciences and Technology, University of Mons, Mons, Belgium.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Belayew
authors.affiliation: PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, Montpellier, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Carnac
authors.affiliation: PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, Montpellier, France.
authors.forename: Dalila
authors.initials: D
authors.lastname: Laoudj-Chenivesse
authors.affiliation: UMR 8126, Univ. Paris-Sud, CNRS, Institut de Cancérologie Gustave-Roussy, Villejuif, France.|LIA1066 Laboratoire Franco-Russe de Recherches en Oncologie, Villejuif, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Lipinski
authors.affiliation: N.K. Koltzov Institute of Developmental Biology, RAS, Moscow, Russia.
authors.forename: Andrei
authors.initials: A
authors.lastname: Vasiliev
authors.affiliation: UMR 8126, Univ. Paris-Sud, CNRS, Institut de Cancérologie Gustave-Roussy, Villejuif, France.|LIA1066 Laboratoire Franco-Russe de Recherches en Oncologie, Villejuif, France.|N.K. Koltzov Institute of Developmental Biology, RAS, Moscow, Russia.
authors.forename: Yegor S
authors.initials: YS
authors.lastname: Vassetzky
mesh_terms: D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D059467:Transcriptome
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; C121257:DUX4L1 protein, human; D018398:Homeodomain Proteins; D019718:Receptors, CXCR4
keywords: CXCR4; DUX4; SDF1; migration; signalling