Gene amplification in mesenchymal stem cells and during differentiation towards adipocytes or osteoblasts
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Nora Corinna Altmayer1,*, Valentina Galata2,*, Nadine Warschburger1, Andreas Keller2, Eckart Meese1,* and Ulrike Fischer1,*
1Department of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany
2Chair of Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany
*These authors contributed equally to this work
Ulrike Fischer, email: [email protected]
Keywords: gene amplification; CDK4; MDM2; osteoblast; adipocyte
Received: May 27, 2017 Accepted: November 01, 2017 Published: December 01, 2017
Gene amplifications are an attribute of tumor cells and have for long time been overlooked in normal cells. A growing number of investigations describe gene amplifications in normal mammalian cells during development and differentiation. Possibly, tumor cells have rescued the gene amplification mechanism as a physiological attribute of stem cells. Here, we investigated human mesenchymal stem cells (hMSCs) for gene amplification using array-CGH, single cell fluorescence in situ hybridization and qPCR. Gene amplifications were detected in mesenchymal stem cells and in mesenchymal stem cells during differentiation towards adipocytes and osteoblasts. Undifferentiated hMSCs harbor 12 amplified chromosomal regions, hMSCs that differentiated towards adipocytes 18 amplified chromosome regions, and hMSCs that differentiate towards osteoblasts 19 amplified regions. Specifically, hMSCs that differentiated towards adipocytes or osteoblasts harbor CDK4 and MDM2 amplifications both of which frequently occur in osteosarcoma and liposarcoma that are both of same cell origin. Beside the amplifications, we identified 36 under-replicated regions in undifferentiated and in differentiating hMSC cells.
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