克隆差异是对连续和长期治疗产生不同反应的原因。

Cell systems Pub Date : 2024-03-20 Epub Date: 2024-02-23 DOI:10.1016/j.cels.2024.01.011
Dylan L Schaff, Aria J Fasse, Phoebe E White, Robert J Vander Velde, Sydney M Shaffer
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引用次数: 0

摘要

癌细胞在单细胞水平上的基因表达存在巨大差异,这可以预测它们是否会对治疗产生耐药性。治疗会延续这种异质性,导致耐药克隆中细胞状态的多样性。然而,目前仍不清楚这些差异是否会导致在采用另一种治疗方法或继续采用同一种治疗方法时产生不同的反应。在这项研究中,我们将单细胞 RNA 测序与条形码结合起来,通过长期和连续的治疗来追踪耐药克隆。我们发现,经过多轮治疗后,同一克隆内的细胞具有相似的基因表达状态。此外,我们还证明,当接受第二次治疗或继续第一次治疗时,单个克隆会有不同的命运,包括生长、存活或死亡。通过确定预测克隆存活的基因表达状态,这项工作为选择针对肿瘤内最具侵袭性的耐药克隆的最佳疗法奠定了基础。本文的同行评审过程透明,其记录见补充信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clonal differences underlie variable responses to sequential and prolonged treatment.

Cancer cells exhibit dramatic differences in gene expression at the single-cell level, which can predict whether they become resistant to treatment. Treatment perpetuates this heterogeneity, resulting in a diversity of cell states among resistant clones. However, it remains unclear whether these differences lead to distinct responses when another treatment is applied or the same treatment is continued. In this study, we combined single-cell RNA sequencing with barcoding to track resistant clones through prolonged and sequential treatments. We found that cells within the same clone have similar gene expression states after multiple rounds of treatment. Moreover, we demonstrated that individual clones have distinct and differing fates, including growth, survival, or death, when subjected to a second treatment or when the first treatment is continued. By identifying gene expression states that predict clone survival, this work provides a foundation for selecting optimal therapies that target the most aggressive resistant clones within a tumor. A record of this paper's transparent peer review process is included in the supplemental information.

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