Potential Marker Genes for Predicting Adipogenic Differentiation of Mesenchymal Stromal Cells

Potential Marker Genes for Predicting Adipogenic Differentiation of Mesenchymal Stromal Cells
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DOI:
10.3390/app9142942
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发表时间:
2019-07-02
影响因子:
2.7
通讯作者:
Kawamoto, Takeshi
Kawamoto, Takeshi
中科院分区:
综合性期刊4区
文献类型:
--
作者:
Kanawa, Masami;Igarashi, Akira;Kawamoto, Takeshi

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间充质基质细胞(MSC)是软结缔组织组织工程的一个有前途的来源。然而,间充质干细胞的分化能力因不同细胞系而异。在这里,我们展示了预测 MSC 成脂潜力的标记基因。为了阐明脂肪诱导前基因表达模式与分化后 MSC 分化水平之间的相关性,我们比较了来自 15 个供体的 15 个 MSC 系(5 个颌 MSC 和 10 个髂骨 MSC)中 95 个基因的 mRNA 水平和 3-磷酸甘油脱氢酶(GPDH)活性。分化前22个基因的表达谱与分化后的GPDH活性显着相关。与分化潜力有限的颌骨 MSC 相比,高效髂骨 MSC 中 22 个基因中有 11 个的表达水平至少高出三倍。此外,ITGA5、CDKN2D 和 CD74 mRNA 表达的三维散点图可以完全区分脂肪生成的强效 MSC 和弱效 MSC。用抗ITGA5抗体处理MSC培养物可减少MSC的成脂分化。总的来说,这些结果表明这三个基因在诱导前的脂肪形成中发挥作用,并且可以作为选择有效的 MSC 进行脂肪形成分化的预测因子。
Mesenchymal stromal cells (MSCs) are a promising source for tissue engineering of soft connective tissues. However, the differentiation capacity of MSCs varies among individual cell lines. Here, we show marker genes to predict the adipogenic potential of MSCs. To clarify the correlation between gene expression patterns before adipogenic induction and the differentiation level of MSCs after differentiation, we compared mRNA levels of 95 genes and glycerol-3-phosphate dehydrogenase (GPDH) activities in 15 MSC lines (five jaw and 10 ilium MSCs) from 15 donors. Expression profiles of 22 genes before differentiation significantly correlated with GPDH activities after differentiation. Expression levels of 11 out of the 22 genes in highly potent ilium MSCs were at least three times higher compared with jaw MSCs, which have limited differentiation potential. Furthermore, three-dimensional scatter plot for mRNA expression of ITGA5, CDKN2D, and CD74 could completely distinguish highly potent MSCs from poorly potent MSCs for adipogenesis. The treatment of MSC cultures with the anti-ITGA5 antibody reduced adipogenic differentiation of MSCs. Collectively, these results suggest that the three genes play a role in adipogenesis before induction and can serve as predictors to select potent MSCs for adipogenic differentiation.