使用CloneSweeper进行多重丰富和追踪血统
bioRxiv : the preprint server for biology
|February 9, 2026
概括
黑色素瘤的耐疗性源于罕见的,先前存在的细胞群,而不是药物诱导的变化. 克隆扫描器技术将这些罕见的血统分离出来,揭示了具有特定分子标记物驱动阻力的原始状态.
科学领域:
- 癌症生物学 癌症生物学
- 基因组学就是基因组学.
- 细胞生物学 细胞生物学
背景情况:
- 治疗耐药性是癌症治疗的一个主要挑战,其起源在先前存在的细胞状态 (原始化) 和药物诱导的变化 (适应) 之间进行了辩论.
- 目前用于单细胞RNA测序 (scRNA-seq) 的谱系条码方法在捕获罕见细胞谱系或同时分离多个特定谱系进行功能分析方面存在局限性.
研究的目的:
- 开发一个新的多重血统追踪平台,CloneSweeper,能够同时分离或丰富多个罕见细胞血统.
- 使用CloneSweeper调查BRAF V600E黑色素瘤中治疗耐药性的起源.
主要方法:
- 开发了CloneSweeper,一个使用双功能条形码进行活细胞分类 (Cas9 gRNA) 和高恢复性scRNA-seq检测 (3' UTR转录) 的平台.
- 将CloneSweeper应用于BRAF V600E黑色素瘤模型,在向治疗治疗之前同时准和丰富21种不同的罕见血统.
- 使用 10x Genomics scRNA-seq 进行丰富细胞群的高分辨率分析.
主要成果:
- 确定BRAF V600E黑色素瘤中向治疗耐药性来自于罕见的多克隆种群,先前存在的血统.
- 在这些耐药血统中,具有遗传性,原始状态的特征,其标志是脱差异化和中酶体标志物升高.
- 证明原始细胞通过AP-1和NF-κB1通路显示高调节的炎症和应激反应信号,而不是静止.
结论:
- CloneSweeper提供了一个强大的框架,用于剖析罕见生物现象背后的分子机制,例如治疗耐药性.
- 在这种黑色素瘤模型中,对向治疗的抵抗是由具有明显分子特征的先前存在的原始细胞群驱动的.
- 这些发现突显了针对这些罕见的,原始细胞状态以克服治疗耐药性的重要性.
更多相关视频
10:55Live Imaging Followed by Single Cell Tracking to Monitor Cell Biology and the Lineage Progression of Multiple Neural Populations
Published on: December 16, 2017
9.2K
08:48Demonstration of Spin-Multiplexed and Direction-Multiplexed All-Dielectric Visible Metaholograms
Published on: September 25, 2020
6.3K
相关概念视频
Lineage Commitment
4.4K
Commitment is the process whereby stem cells:
4.4K
Genome Size and the Evolution of New Genes
9.2K
While every living organism has a genome of some kind (be it RNA, or DNA), there is considerable variation in the sizes of these blueprints. One major factor that impacts genome size is whether the organism is prokaryotic or eukaryotic. In prokaryotes, the genome contains little to no non-coding sequence, such that genes are tightly clustered in groups or operons sequentially along the chromosome. Conversely, the genes in eukaryotes are punctuated by long stretches of non-coding sequence.
9.2K
The Soil Ecosystem
24.9K
Plants obtain inorganic minerals and water from the soil, which acts as a natural medium for land plants. The composition and quality of soil depend not only on the chemical constituents but also on the presence of living organisms. In general, soils contain three major components:
24.9K
Seedless Vascular Plants
67.3K
Seedless Vascular Plants Were the First Tall Plants on Earth
67.3K
Classification of Skeletal Muscle Fibers
59.6K
Skeletal muscles continuously produce ATP to provide the energy that enables muscle contractions. Skeletal muscle fibers can be categorized into three types based on differences in their contraction speed and how they produce ATP, as well as physical differences related to these factors. Most human muscles contain all three muscle fiber types, albeit in varying proportions.
Slow-Twitch Muscle Fibers
Slow oxidative, muscle fibers appear red due to large numbers of capillaries and high levels of...
Slow-Twitch Muscle Fibers
Slow oxidative, muscle fibers appear red due to large numbers of capillaries and high levels of...
59.6K
Additional Subnuclear Structures
5.4K
The eukaryotic nucleus is a double membrane-bound organelle that contains nearly all of the cell’s genetic material in the form of chromosomes. It is rightly called the “brain” of the cell as it shoulders the responsibility of responding to various physiological processes, stress, altered metabolic conditions, and other cellular signals.
The nucleus contains many membrane-less subnuclear organelles or nuclear bodies, such as nucleoli, Cajal bodies, speckles,...
The nucleus contains many membrane-less subnuclear organelles or nuclear bodies, such as nucleoli, Cajal bodies, speckles,...
5.4K
