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剂量和时间依赖性上皮-间质谱系的比较单细胞转录组

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

作者信息

Panchy Nicholas, Watanabe Kazuhide, Takahashi Masataka, Willems Andrew, Hong Tian

机构信息

Department of Biochemistry & Cellular and Molecular Biology. The University of Tennessee, Knoxville, Knoxville, TN 37996, USA.

RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.

出版信息

NAR Genom Bioinform. 2022 Sep 21;4(3):lqac072. doi: 10.1093/nargab/lqac072. eCollection 2022 Sep.

DOI:10.1093/nargab/lqac072
PMID:36159174
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9492285/
Abstract

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 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 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.

摘要

上皮-间质转化（EMT）是一个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了中间EMT状态，但以往的研究集中在单剂量信号的时间依赖性反应上；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，我们对用多剂量转化生长因子-β（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在接近稳态时具有多个中间状态。对剂量和时间依赖性EMT转录组的比较表明，剂量依赖性数据能够更高灵敏度地检测与EMT相关的基因。我们鉴定出了时间依赖性EMT特有的细胞簇，反映了细胞向稳定状态的转变。结合剂量和时间依赖性细胞簇可为癌症患者提供准确的预后。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，以及两种单细胞实验的互补信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab9/9492285/db8665b1c8f4/lqac072fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab9/9492285/e5f5f6c26587/lqac072fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab9/9492285/63a66216ea30/lqac072fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab9/9492285/aa56b636dc3e/lqac072fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab9/9492285/99b7166a4efc/lqac072fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab9/9492285/db8665b1c8f4/lqac072fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab9/9492285/e5f5f6c26587/lqac072fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab9/9492285/63a66216ea30/lqac072fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab9/9492285/aa56b636dc3e/lqac072fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab9/9492285/99b7166a4efc/lqac072fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab9/9492285/db8665b1c8f4/lqac072fig5.jpg

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