Gene amplification in mesenchymal stem cells and during differentiation towards adipocytes or osteoblasts
Gene amplification in mesenchymal stem cells and during differentiation towards adipocytes or osteoblasts
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DOI：
10.18632/oncotarget.22804
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发表时间：
2018-01-05
期刊：
影响因子：
--
通讯作者：
Fischer, Ulrike
中科院分区：
文献类型：
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作者：
Altmayer, Nora Corinna;Galata, Valentina;Fischer, Ulrike
基因扩增是肿瘤细胞的一个属性，在正常细胞中长期被忽视。越来越多的研究描述了正常哺乳动物细胞在发育和分化过程中的基因扩增。可能，肿瘤细胞拯救了基因扩增机制作为干细胞的生理属性。在这里，我们研究了人骨髓间充质干细胞（hMSCs）的基因扩增使用阵列CGH，单细胞荧光原位杂交和qPCR。在间充质干细胞和向脂肪细胞和成骨细胞分化的间充质干细胞中检测到基因扩增。未分化的hMSC具有12个扩增的染色体区域，向脂肪细胞分化的hMSC具有18个扩增的染色体区域，向成骨细胞分化的hMSC具有19个扩增的染色体区域。具体而言，向脂肪细胞或成骨细胞分化的hMSC具有CDK4和MDM2扩增，这两者经常发生在相同细胞来源的骨肉瘤和脂肪肉瘤中。除了扩增，我们还在未分化和分化的hMSC细胞中鉴定了36个复制不足的区域。
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.