Comparative single-cell transcriptomes of dose and time dependent epithelial-mesenchymal spectrums.

Comparative single-cell transcriptomes of dose and time dependent epithelial-mesenchymal spectrums.
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DOI:
10.1093/nargab/lqac072
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发表时间:
2022-09
影响因子:
4.6
通讯作者:
Hong, Tian
Hong, Tian
中科院分区:
其他
文献类型:
--
作者:
Panchy, Nicholas;Watanabe, Kazuhide;Takahashi, Masataka;Willems, Andrew;Hong, Tian

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上皮-间充质转化(EMT)是一种参与发育和疾病进展的细胞过程。在肿瘤和纤维化组织中观察到中间EMT状态,但以前的体外研究集中在单剂量信号的时间依赖性反应;尚不清楚单细胞转录组是否支持在疾病中观察到的稳定中间体。在这里,我们对用多剂量TGF-β处理的人乳腺上皮细胞进行了单细胞RNA测序。我们发现,剂量依赖性EMT港口多个中间态在近稳态。剂量依赖性和时间依赖性EMT转录组的比较显示,剂量依赖性数据使得检测EMT相关基因的灵敏度更高。我们确定了时间依赖性EMT所特有的细胞簇,反映了细胞在稳定状态的过程中。结合剂量和时间依赖性细胞簇,可以准确预测癌症患者的预后。我们的转录组数据和分析揭示了单细胞分辨率下稳定的EMT连续体,以及两种类型的单细胞实验的互补信息。
Epithelial–mesenchymal transition (EMT) is a cellular process involved in development and disease progression. Intermediate EMT states were observed in tumors and fibrotic tissues, but previous in vitro studies focused on time-dependent responses with single doses of signals; it was unclear whether single-cell transcriptomes support stable intermediates observed in diseases. Here, we performed single-cell RNA-sequencing with human mammary epithelial cells treated with multiple doses of TGF-β. We found that dose-dependent EMT harbors multiple intermediate states at nearly steady state. Comparisons of dose- and time-dependent EMT transcriptomes revealed that the dose-dependent data enable higher sensitivity to detect genes associated with EMT. We identified cell clusters unique to time-dependent EMT, reflecting cells en route to stable states. Combining dose- and time-dependent cell clusters gave rise to accurate prognosis for cancer patients. Our transcriptomic data and analyses uncover a stable EMT continuum at the single-cell resolution, and complementary information of two types of single-cell experiments.
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