一个多重单细胞RNA-Seq药物转录学管道用于药物发现
Alice Dini1, Harlan Barker1,2, Emilia Piki1
1Disease Networks Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
Nature chemical biology
|November 1, 2024
概括
我们开发了一种使用单细胞RNA测序在癌细胞中高通量药物查的新方法. 这种方法揭示了卵巢癌药物耐药性的反循环,这种反循环可以通过组合疗法克服.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 了解癌症药物反应中的基因调节动态至关重要.
- 目前的方法缺乏高通量单细胞分辨率的药物转录组学.
研究的目的:
- 开发和验证一个高通量药物转录基因分析分析管道.
- 在单细胞分辨率下探索高度血清性卵巢癌 (HGSOC) 的药物反应和耐药性机制.
主要方法:
- 活细胞条形码与抗体-寡核酸合物.
- 96倍复数单细胞RNA测序与药物查相结合.
- 用45种药物治疗的HGSOC细胞中转录景观的分析.
主要成果:
- 确定了一种药物耐药反循环,涉及PI3K-AKT-mTOR抑制剂,EGFR激活和CAV1上调.
- 证明PI3K-AKT-mTOR和EGFR的协同抑制可以通过特定的生物标志物克服HGSOC中的抵抗.
- 展示了对各种药物类别的细胞反应的异质性.
结论:
- 开发的管道能够实现高通量,单细胞药物转录学概况.
- 揭示了HGSOC药物耐药性的可向反循环.
- 这种工作流促进了针对癌症治疗测试的个性化医疗方法.
相关概念视频
RNA-seq
9.8K
RNA sequencing, or RNA-Seq, is a high-throughput sequencing technology used to study the transcriptome of a cell. Transcriptomics helps to interpret the functional elements of a genome and identify the molecular constituents of an organism. Additionally, it also helps in understanding the development of an organism and the occurrence of diseases.
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while...
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while...
9.8K
Ribosome Profiling
3.5K
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
3.5K


