Cells Respond to Distinct Nanoparticle Properties with Multiple Strategies As Revealed by Single-Cell RNA-Seq.
Cells Respond to Distinct Nanoparticle Properties with Multiple Strategies As Revealed by Single-Cell RNA-Seq.
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DOI：
10.1021/acsnano.6b05452
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发表时间：
2016-10
期刊：
影响因子：
17.1
通讯作者：
H. Mitchell;L. M. Markillie;W. Chrisler;Matthew J. Gaffrey;Dehong Hu;C. Szymanski;Yumei Xie;Eric S. Melby;A. Dohnalkova;Ronald C. Taylor;Eva K Grate;S. Cooley;J. Mcdermott;A. Heredia-Langner;G. Orr
中科院分区：
文献类型：
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作者：
H. Mitchell;L. M. Markillie;W. Chrisler;Matthew J. Gaffrey;Dehong Hu;C. Szymanski;Yumei Xie;Eric S. Melby;A. Dohnalkova;Ronald C. Taylor;Eva K Grate;S. Cooley;J. Mcdermott;A. Heredia-Langner;G. Orr
不同的纳米颗粒（NP）特性对细胞反应和最终人类健康的影响尚不清楚。这种差距部分是由于在所研究的细胞中实现均匀纳米颗粒负载的实验困难，从而产生异质群体，其中一些细胞“超载”，而其他细胞负载很少或没有纳米颗粒。然而，基因表达研究已经在整个人群中进行，识别了通用反应，但由于许多细胞的信号平均而丢失了独特的反应，每个细胞都携带不同的负载。在这里，我们将单细胞 RNA 测序应用于携带规定负载的胺化或羧化量子点 (QD) 的肺泡上皮细胞，分别显示出较高或较低的毒性。有趣的是，负载较低的细胞会采取多种策略做出反应，其中大多数是上调过程，但这些过程对于每种 QD 类型来说都是一致且独特的。相比之下，携带较高负载的细胞反应更均匀，大部分 QD 类型共享的下调过程。胺化量子点独特的策略显示出对应激反应的强烈上调，在某些情况下还与细胞周期、蛋白质合成和细胞器活性的调节相结合。相比之下，羧化量子点特有的策略显示 DNA 修复和 RNA 活性上调，细胞分裂调节减弱，在某些情况下还上调应激反应和 ATP 相关功能。总之，我们的研究表明，较高的 NP 负载会将细胞锁定为统一的反应，主要是细胞过程的关闭，而较低的负载允许对每种 NP 类型做出独特的反应，从而对 NP 损伤进行更多样化的主动防御或修复。
The impact of distinct nanoparticle (NP) properties on cellular response and ultimately human health is unclear. This gap is partially due to experimental difficulties in achieving uniform NP loads in the studied cells, creating heterogeneous populations with some cells "overloaded" while other cells are loaded with few or no NPs. Yet gene expression studies have been conducted in the population as a whole, identifying generic responses, while missing unique responses due to signal averaging across many cells, each carrying different loads. Here, we applied single-cell RNA-Seq to alveolar epithelial cells carrying defined loads of aminated or carboxylated quantum dots (QDs), showing higher or lower toxicity, respectively. Interestingly, cells carrying lower loads responded with multiple strategies, mostly with up-regulated processes, which were nonetheless coherent and unique to each QD type. In contrast, cells carrying higher loads responded more uniformly, with mostly down-regulated processes that were shared across QD types. Strategies unique to aminated QDs showed strong up-regulation of stress responses, coupled in some cases with regulation of cell cycle, protein synthesis, and organelle activities. In contrast, strategies unique to carboxylated QDs showed up-regulation of DNA repair and RNA activities and decreased regulation of cell division, coupled in some cases with up-regulation of stress responses and ATP-related functions. Together, our studies suggest scenarios where higher NP loads lock cells into uniform responses, mostly shutdown of cellular processes, whereas lower loads allow for unique responses to each NP type that are more diversified proactive defenses or repairs of the NP insults.