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Gene amplification in mesenchymal stem cells and during differentiation towards adipocytes or osteoblasts
Nora Corinna Altmayer1, Valentina Galata2, Nadine Warschburger1
1Department of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany.
Oncotarget
|February 9, 2018
Summary
Gene amplifications, previously overlooked in normal cells, are found in human mesenchymal stem cells (hMSCs) and during their differentiation. These findings suggest stem cells may utilize gene amplification mechanisms.
Area of Science:
- Genetics
- Cell Biology
- Developmental Biology
Background:
- Gene amplifications are a hallmark of cancer cells, but their presence in normal cells is increasingly recognized.
- Normal mammalian cells, particularly during development and differentiation, exhibit gene amplifications.
- Tumor cells may have co-opted gene amplification mechanisms from physiological processes in stem cells.
Purpose of the Study:
- To investigate the presence and nature of gene amplifications in human mesenchymal stem cells (hMSCs).
- To examine gene amplification patterns in hMSCs during differentiation into adipocytes and osteoblasts.
- To identify specific amplified genes and their potential relevance to cancer biology.
Main Methods:
- Utilized array comparative genomic hybridization (array-CGH) to detect chromosomal copy number variations.
- Employed single-cell fluorescence in situ hybridization (FISH) for precise localization of amplifications.
- Performed quantitative polymerase chain reaction (qPCR) to validate and quantify amplified regions.
Main Results:
- Detected gene amplifications in undifferentiated hMSCs (12 regions), differentiating adipocytes (18 regions), and differentiating osteoblasts (19 regions).
- Identified specific amplifications of *CDK4* and *MDM2* in differentiating hMSCs, genes frequently amplified in related cancers (osteosarcoma, liposarcoma).
- Discovered 36 under-replicated chromosomal regions in both undifferentiated and differentiating hMSCs.
Conclusions:
- Gene amplifications are present in normal human mesenchymal stem cells and are dynamically altered during differentiation.
- The findings support the hypothesis that gene amplification is a conserved mechanism with roles in both normal stem cell biology and cancer.
- Specific amplifications in hMSCs mirror those found in related bone and fat-derived tumors, highlighting a potential link between stem cell processes and oncogenesis.
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