Specific amplifications and copy number decreases during human neural stem cells differentiation towards astrocytes, neurons and oligodendrocytes
Specific amplifications and copy number decreases during human neural stem cells differentiation towards astrocytes, neurons and oligodendrocytes
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DOI：
10.18632/oncotarget.15980
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发表时间：
2017-04-18
期刊：
影响因子：
--
通讯作者：
Meese, Eckart
中科院分区：
文献类型：
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作者：
Fischer, Ulrike;Kim, Ella;Meese, Eckart
越来越多的证据表明，基因扩增是正常细胞在发育和分化过程中的一个属性。在神经前体细胞分化过程中，一半的基因组参与扩增过程。为了回答特异性扩增如何在不同阶段和不同分化谱系中发生的问题，我们分析了诱导向星形胶质细胞、神经元和少突胶质细胞分化的人神经干细胞中的基因CDK4、MDM2、EGFR、GINS 2、GFAP、TP53、DDB 1和MDM4。我们在未分化的神经干细胞和祖细胞以及诱导分化的细胞中发现了八个分析基因中每一个的特异性扩增模式。在贴壁生长的神经干细胞和球形生长的细胞之间也发现了不同的扩增模式。最常扩增的基因是MDM 2和CDK 4，后者在所有分析阶段在所有三个谱系中扩增。在四个胶质瘤干细胞样细胞中也发现了所分析基因的扩增。干细胞和肿瘤干细胞的组合扩增数据可以帮助确定肿瘤起源处的细胞群。此外，我们检测到MDM4在特定分化阶段的基因拷贝减少最频繁。本研究显示了在分化过程中特定时间窗口内的特定干细胞群中的特异性扩增模式，表明在人神经干细胞和祖细胞的分化过程中扩增以有序的顺序发生。
There is growing evidence that gene amplifications are an attribute of normal cells during development and differentiation. During neural progenitor cell differentiation half of the genome is involved in amplification process. To answer the question how specific amplifications occur at different stages and in different lineages of differentiation we analyzed the genes CDK4, MDM2, EGFR, GINS2, GFAP, TP53, DDB1 and MDM4 in human neural stem cells that were induced to differentiate towards astrocytes, neurons and oligodendrocytes. We found specific amplification pattern for each of the eight analyzed genes both in undifferentiated neural stem and progenitor cells and in cells that were induced for differentiation. Different amplification patterns were also found between adherently grown neural stem cells and cells that were grown as spheres. The most frequently amplified genes were MDM2 and CDK4 with the latter amplified in all three lineages at all analyzed stages. Amplification of the analyzed genes was also found in four glioma stem-like cells. The combined amplification data of stem cells and of tumor stem cells can help to define cell populations at the origin of the tumor. Furthermore, we detected a decrease of gene copies at specific differentiation stages most frequently for MDM4. This study shows specific amplification pattern in defined stem cell populations within specific time windows during differentiation processes indicating that amplifications occur in an orderly sequence during the differentiation of human neural stem and progenitor cells.