Dux4 controls migration of mesenchymal stem cells through the Cxcr4-Sdf1 axis
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Petr Dmitriev1,2,*, Ekaterina Kiseleva2,3,*, Olga Kharchenko2,3, Evgeny Ivashkin2,3, Andrei Pichugin2,3,7, Philippe Dessen4, Thomas Robert4, Frédérique Coppée5, Alexandra Belayew5, Gilles Carnac6, Dalila Laoudj-Chenivesse6, Marc Lipinski1,2, Andrei Vasiliev3, Yegor S. Vassetzky1,2,3
1UMR 8126, Univ. Paris-Sud, CNRS, Institut de Cancérologie Gustave-Roussy, Villejuif, France
2LIA1066 Laboratoire Franco-Russe de Recherches en Oncologie, Villejuif, France
3N.K. Koltzov Institute of Developmental Biology, RAS, Moscow, Russia
4Functional Genomics Unit, Institut de Cancérologie Gustave-Roussy, Villejuif, France
5Laboratory of Molecular Biology, Research Institute for Health Sciences and Technology, University of Mons, Mons, Belgium
6PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, Montpellier, France
7Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia
*These authors contributed equally to this work
Yegor S. Vassetzky, email: firstname.lastname@example.org
Keywords: DUX4, CXCR4, SDF1, signalling, migration
Received: April 01, 2016 Accepted: August 10, 2016 Published: August 18, 2016
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.
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