Widespread changes in transcriptome profile of human mesenchymal stem cells induced by two-dimensional nanosilicates.
Widespread changes in transcriptome profile of human mesenchymal stem cells induced by two-dimensional nanosilicates.
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DOI：
10.1073/pnas.1716164115
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发表时间：
2018-04-24
影响因子：
11.1
通讯作者：
Gaharwar AK
中科院分区：
文献类型：
--
作者：
Carrow JK;Cross LM;Reese RW;Jaiswal MK;Gregory CA;Kaunas R;Singh I;Gaharwar AK
我们展示了使用下一代测序技术（RNA-seq）来了解二维纳米材料在全转录组水平上对人类干细胞的影响。我们的研究结果确定了4,000多个受到显著影响的基因，并且纳米颗粒处理触发了几种生物物理和生物化学途径。我们希望这种系统的方法来了解由于纳米材料暴露引起的基因表达的广泛变化，这是开发用于生物医学应用的新生物活性材料的关键。二维纳米材料是石墨烯、纳米粘土、过渡金属二硫属化物（TMD）和过渡金属氧化物（TMOs）等一类新型材料，由于其相对于宏观尺度材料的独特性质，已成为新一代材料。然而，对暴露于这些纳米材料后的转录组动力学知之甚少。在这里，我们研究了2D纳米硅酸盐，层状粘土，与人类间充质干细胞（hMSCs）在全转录组水平的高通量测序（RNA-seq）的相互作用。通过监测转录组谱的变化来分析细胞-纳米硅酸盐相互作用，揭示了纳米硅酸盐触发的关键生物物理和生物化学细胞途径。由于纳米硅酸盐暴露，观察到基因的广泛改变，因为超过4，000个基因差异表达。mRNA表达水平的变化揭示了网格蛋白介导的纳米硅酸盐的内吞作用。纳米硅酸盐附着于细胞膜和随后的细胞内化激活了应激反应途径，如丝裂原活化蛋白激酶（MAPK），随后将hMSC分化为成骨和软骨细胞系。这项研究提供了对纳米材料引发的表面介导的细胞信号传导的作用的转录组学见解，并能够开发基于纳米材料的再生医学疗法。这种理解纳米材料-细胞相互作用的方法说明了转录组学特征的变化如何预测纳米材料处理后的下游效应。
We demonstrate the use of next-generation sequencing technology (RNA-seq) to understand the effect of a two-dimensional nanomaterial on human stem cells at the whole-transcriptome level. Our results identify more than 4,000 genes that are significantly affected, and several biophysical and biochemical pathways are triggered by nanoparticle treatment. We expect that this systematic approach to understand widespread changes in gene expression due to nanomaterial exposure is key to develop new bioactive materials for biomedical applications. Two-dimensional nanomaterials, an ultrathin class of materials such as graphene, nanoclays, transition metal dichalcogenides (TMDs), and transition metal oxides (TMOs), have emerged as a new generation of materials due to their unique properties relative to macroscale counterparts. However, little is known about the transcriptome dynamics following exposure to these nanomaterials. Here, we investigate the interactions of 2D nanosilicates, a layered clay, with human mesenchymal stem cells (hMSCs) at the whole-transcriptome level by high-throughput sequencing (RNA-seq). Analysis of cell–nanosilicate interactions by monitoring changes in transcriptome profile uncovered key biophysical and biochemical cellular pathways triggered by nanosilicates. A widespread alteration of genes was observed due to nanosilicate exposure as more than 4,000 genes were differentially expressed. The change in mRNA expression levels revealed clathrin-mediated endocytosis of nanosilicates. Nanosilicate attachment to the cell membrane and subsequent cellular internalization activated stress-responsive pathways such as mitogen-activated protein kinase (MAPK), which subsequently directed hMSC differentiation toward osteogenic and chondrogenic lineages. This study provides transcriptomic insight on the role of surface-mediated cellular signaling triggered by nanomaterials and enables development of nanomaterials-based therapeutics for regenerative medicine. This approach in understanding nanomaterial–cell interactions illustrates how change in transcriptomic profile can predict downstream effects following nanomaterial treatment.
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影响因子：
6.6
作者：
Han, Pingping;Wu, Chengtie;Xiao, Yin
通讯作者：
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影响因子：
29.4
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影响因子：
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作者：
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48
作者：
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DOI：
10.1073/pnas.0505259102
发表时间：
2005-11-29
影响因子：
11.1
作者：
Clément-Lacroix, P;Ai, MR;Rawadi, G
通讯作者：
Rawadi, G