Effects of Ectopic Nanog and Oct4 Overexpression on Mesenchymal Stem Cells
Effects of Ectopic Nanog and Oct4 Overexpression on Mesenchymal Stem Cells
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DOI：
10.1089/scd.2008.0335
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发表时间：
2009-09-01
影响因子：
4
通讯作者：
Lim, Bing
中科院分区：
文献类型：
--
作者：
Liu, Tong Ming;Wu, Ying Nan;Lim, Bing
间充质干细胞（MSC）代表了已经处于临床应用各个阶段的多能细胞的来源。然而，MSC在组织工程中的应用在很大程度上由于其局限性而受到阻碍，包括低增殖、有限的寿命和在离体扩增期间其干细胞性质的逐渐丧失。Nanog和Oct 4是未分化胚胎干细胞（ESC）多能性和自我更新表型所必需的关键转录因子。为了确定Nanog和Oct 4是否改善人骨髓-MSC质量，我们因此使用慢病毒系统建立了稳定的Nanog和Oct 4过表达MSC，并表明这促进了细胞增殖并增强了MSC的集落形成。在分化的MSC、Nanog和Oct 4中，过表达对MSC的脂肪形成具有匡威的影响，Nanog过表达减缓脂肪形成，而Oct 4过表达促进脂肪形成。Nanog和Oct 4过表达均改善软骨形成。微阵列数据显示，在过表达Nanog和Oct 4的未分化MSC中，转录靶点存在许多差异。这些结果提供了深入了解干细胞的干细胞相关基因的遗传修饰的改善。
Mesenchymal stem cells (MSCs) represent a source of pluripotent cells that are already in various phases of clinical application. However, the use of MSCs in tissue engineering has been hampered largely due to their limitations, including low proliferation, finite life span, and gradual loss of their stem cell properties during ex vivo expansion. Nanog and Oct4 are key transcription factors essential to the pluripotent and self-renewing phenotypes of undifferentiated embryonic stem cells (ESCs). To determine whether Nanog and Oct4 improve human bone marrow-MSC quality, we therefore established stable Nanog and Oct4 overexpressing MSCs using a lentiviral system and showed that this promoted cell proliferation and enhanced colony formation of MSCs. In differentiating MSCs, Nanog, and Oct4, overexpression had converse effects on adipogenesis of MSCs and Nanog overexpression slowed down adipogenesis, whereas Oct4 overexpression improved adipogenesis. Nanog and Oct4 overexpression both improved chondrogenesis. Microarray data showed many differences in transcriptional targets in undifferentiated MSCs overexpressing Nanog and Oct4. These results provide insight into the improvement of the stemness of MSCs by genetic modification with stemness-related genes.