Phenotypic, Genomic, and Transcriptomic Heterogeneity in a Pancreatic Cancer Cell Line.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-10-01 Epub Date: 2024-05-04 DOI:10.1097/MPA.0000000000002371

Gengqiang Xie, Liting Zhang, Olalekan H Usman, Sampath Kumar, Chaity Modak, Dhenu Patel, Megan Kavanaugh, Xian Mallory, Yue Julia Wang, Jerome Irianto

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Abstract

Objective: To evaluate the suitability of the MIA PaCa-2 cell line for studying pancreatic cancer intratumor heterogeneity, we aim to further characterize the nature of MIA PaCa-2 cells' phenotypic, genomic, and transcriptomic heterogeneity.

Materials and methods: MIA PaCa-2 single-cell clones were established through flow cytometry. For the phenotypic study, we quantified the cellular morphology, proliferation rate, migration potential, and drug sensitivity of the clones. The chromosome copy number and transcriptomic profiles were quantified using SNPa and RNA-seq, respectively.

Results: Four MIA PaCa-2 clones showed distinctive phenotypes, with differences in cellular morphology, proliferation rate, migration potential, and drug sensitivity. We also observed a degree of genomic variations between these clones in form of chromosome copy number alterations and single nucleotide variations, suggesting the genomic heterogeneity of the population, and the intrinsic genomic instability of MIA PaCa-2 cells. Lastly, transcriptomic analysis of the clones also revealed gene expression profile differences between the clones, including the uniquely regulated ITGAV , which dictates the morphology of MIA PaCa-2 clones.

Conclusions: MIA PaCa-2 is comprised of cells with distinctive phenotypes, heterogeneous genomes, and differential transcriptomic profiles, suggesting its suitability as a model to study the underlying mechanisms behind pancreatic cancer heterogeneity.

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胰腺癌细胞系的表型、基因组和转录组异质性。

研究目的为了评估 MIA PaCa-2 细胞系是否适合用于研究胰腺癌瘤内异质性，我们旨在进一步确定 MIA PaCa-2 细胞的表型、基因组和转录组异质性的性质：方法：通过流式细胞术建立 MIA PaCa-2 单细胞克隆。在表型研究中，我们对克隆细胞的形态、增殖率、迁移潜力和药物敏感性进行了量化。染色体拷贝数和转录组图谱分别通过 SNPa 和 RNA-seq 进行量化：结果：四个MIA PaCa-2克隆表现出独特的表型，在细胞形态、增殖率、迁移潜力和药物敏感性方面存在差异。我们还观察到这些克隆之间存在一定程度的基因组变异，表现为染色体拷贝数改变和单核苷酸变异，这表明该群体存在基因组异质性，以及 MIA PaCa-2 细胞内在的基因组不稳定性。最后，克隆的转录组分析也揭示了克隆间基因表达谱的差异，包括独特调控的ITGAV，它决定了MIA PaCa-2克隆的形态：结论：MIA PaCa-2由具有独特表型、异质性基因组和差异转录组谱的细胞组成，这表明它适合作为研究胰腺癌异质性背后潜在机制的模型。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.