Dux4 controls migration of mesenchymal stem cells through the Cxcr4-Sdf1 axis

被引：25

作者：

Dmitriev, Petr ^{[1
,2
]}

Kiseleva, Ekaterina ^{[2
,3
]}

Kharchenko, Olga ^{[2
,3
]}

Ivashkin, Evgeny ^{[2
,3
]}

Pichugin, Andrei ^{[2
,3
,7
]}

Dessen, Philippe ^{[4
]}

Robert, Thomas ^{[4
]}

Coppee, Frederique ^{[5
]}

Belayew, Alexandra ^{[5
]}

Carnac, Gilles ^{[6
]}

Laoudj-Chenivesse, Dalila ^{[6
]}

Lipinski, Marc ^{[1
,2
]}

Vasiliev, Andrei ^{[3
]}

Vassetzky, Yegor S. ^{[1
,2
,3
]}

机构：

[1] Univ Paris Sud, CNRS, Inst Cancerol Gustave Roussy, UMR 8126, Villejuif, France

[2] LIA1066 Lab Francorusse Rech Oncol, Villejuif, France

[3] RAS, NK Koltzov Inst Dev Biol, Moscow, Russia

[4] Inst Cancerol Gustave Roussy, Funct Genom Unit, Villejuif, France

[5] Univ Mons, Res Inst Hlth Sci & Technol, Mol Biol Lab, Mons, Belgium

[6] Univ Montpellier, CNRS UMR 9214, INSERM U1046, PhyMedExp, Montpellier, France

[7] Peter Great St Petersburg Polytech Univ, St Petersburg, Russia

来源：

ONCOTARGET | 2016年 / 7卷 / 40期

关键词：

DUX4; CXCR4; SDF1; signalling; migration; FACIOSCAPULOHUMERAL MUSCULAR-DYSTROPHY; CHEMOKINE RECEPTOR CXCR4; DOUBLE HOMEOBOX GENE; FSHD CANDIDATE GENE; COPY NUMBER; BONE-MARROW; KEY PLAYERS; IN-VITRO; EXPRESSION; DIFFERENTIATION;

D O I：

10.18632/oncotarget.11368

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：65090 / 65108

页数：19

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