小柯机器人

美国宾夕法尼亚大学Arjun Raj等研究人员合作发现，药物治疗同种癌细胞时会出现不同的克隆命运。该项研究成果于2023年7月19日在线发表在《自然》杂志上。

研究人员开发并应用了FateMap（一种将DNA条形码与单细胞RNA测序相结合的框架）来揭示数十万暴露于抗癌疗法的克隆的命运。研究人员发现，从单细胞衍生的癌细胞中产生的耐药克隆在分子、形态和功能上具有不同的耐药类型。这些耐药类型在很大程度上是由添加药物前细胞间的分子差异而非外在因素预先决定的。药物剂量和类型的改变会改变初始细胞的耐药类型，导致某些耐药类型的产生和消除。患者样本显示，临床上存在这些耐药类型的证据。

研究人员在几种单细胞衍生的癌症细胞系和接受多种药物治疗的细胞类型中观察到了耐药类型的多样性。耐药类型的多样性是细胞内在状态变化的结果，这可能是对外界线索反应的通用特征。

据介绍，即使在基因完全相同的癌细胞中，也经常会有一小部分细胞产生抗药性。初始群体中极少数单个细胞的分子差异会使某些细胞对治疗产生耐药性；然而，人们对耐药性结果的可变性知之甚少。

附：英文原文

Title: Diverse clonal fates emerge upon drug treatment of homogeneous cancer cells

Author: Goyal, Yogesh, Busch, Gianna T., Pillai, Maalavika, Li, Jingxin, Boe, Ryan H., Grody, Emanuelle I., Chelvanambi, Manoj, Dardani, Ian P., Emert, Benjamin, Bodkin, Nicholas, Braun, Jonas, Fingerman, Dylan, Kaur, Amanpreet, Jain, Naveen, Ravindran, Pavithran T., Mellis, Ian A., Kiani, Karun, Alicea, Gretchen M., Fane, Mitchell E., Ahmed, Syeda Subia, Li, Haiyin, Chen, Yeqing, Chai, Cedric, Kaster, Jessica, Witt, Russell G., Lazcano, Rossana, Ingram, Davis R., Johnson, Sarah B., Wani, Khalida, Dunagin, Margaret C., Lazar, Alexander J., Weeraratna, Ashani T., Wargo, Jennifer A., Herlyn, Meenhard, Raj, Arjun

Issue&Volume: 2023-07-19

Abstract: Even among genetically identical cancer cells, resistance to therapy frequently emerges from a small subset of those cells1,2,3,4,5,6,7. Molecular differences in rare individual cells in the initial population enable certain cells to become resistant to therapy7,8,9; however, comparatively little is known about the variability in the resistance outcomes. Here we develop and apply FateMap, a framework that combines DNA barcoding with single-cell RNA sequencing, to reveal the fates of hundreds of thousands of clones exposed to anti-cancer therapies. We show that resistant clones emerging from single-cell-derived cancer cells adopt molecularly, morphologically and functionally distinct resistant types. These resistant types are largely predetermined by molecular differences between cells before drug addition and not by extrinsic factors. Changes in the dose and type of drug can switch the resistant type of an initial cell, resulting in the generation and elimination of certain resistant types. Samples from patients show evidence for the existence of these resistant types in a clinical context. We observed diversity in resistant types across several single-cell-derived cancer cell lines and cell types treated with a variety of drugs. The diversity of resistant types as a result of the variability in intrinsic cell states may be a generic feature of responses to external cues.

DOI: 10.1038/s41586-023-06342-8

Source: https://www.nature.com/articles/s41586-023-06342-8

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html