大规模的单细胞分析和in silico扰动揭示了HCC的动态演变:从启动到治疗向
Peng Xia1, Si Shuang1, Daosen Fu1
1Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
NPJ precision oncology
|January 30, 2026
概括
肝细胞癌 (HCC) 的异质性驱动治疗耐药性. 这项研究绘制了HCC细胞生态系统的地图,揭示了不同的恶性细胞状态和微环境相互作用,为改善患者结果提供了新的治疗点.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 细胞生物学 细胞生物学
背景情况:
- 肝细胞癌 (HCC) 呈现出显著的内和微环境异质性,这对有效治疗构成了重大挑战.
- 了解HCC生态系统中的复杂细胞相互作用对于开发向疗法至关重要.
研究的目的:
- 系统地剖析推动肝细胞癌 (HCC) 进展的细胞生态系统,使用集成的单细胞转录学和空间分析.
- 为了识别不同的恶性细胞状态及其相关的微环境.
- 发现HCC的新型治疗脆弱性和依赖性.
主要方法:
- 整合了来自正常肝脏,原发性瘤,门静脉瘤血栓 (PVTT) 和转移性淋巴结 (MLN) 的单细胞转录组数据.
- 空间分析的应用,用于绘制细胞生态系统和结构结构的地图.
- 使用Geneformer进行虚拟淘汰选,以识别关键依赖.
主要成果:
- 恶性肝细胞被分为四个转录元程序 (Diff-Metabolic,Prolif-Stress,MYC-Biosynth-Immune,EMT-Inflammatory),具有不同的临床轨迹和治疗脆弱性,包括对索拉芬尼布的耐药性.
- 在瘤进展过程中观察到免疫抑制性巨细胞群的扩大 (Macro-SPP1,Macro-TREM2).
- 空间映射显示了由特定的内皮细胞 (Endo-ESM1) 和纤维细胞 (Fib-POSTN/Fib-CD36) 群体形成的TGFβ丰富的,与侵袭性瘤细胞状态相关.
- 确定HSP90B1为HCC进展必不可少的融合依赖性,并与低生存率相关.
结论:
- 这本综合图谱为了解HCC瘤内在状态和微环境依赖性提供了一个全面的框架.
- 已识别的细胞状态和 stromal 利基代表了新型治疗策略在HCC.新的潜在目标.
- 准HSP90B1可能是克服肝细胞癌治疗耐药性的有希望的方法.
更多相关视频
07:14Live Cell Imaging to Assess the Dynamics of Metaphase Timing and Cell Fate Following Mitotic Spindle Perturbations
Published on: September 20, 2019
8.7K
05:57Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function
Published on: April 26, 2024
875
相关概念视频
The Evidence for Evolution
48.1K
Genetic variations accumulating within populations over generations give rise to biological evolution. Evolutionary changes can result in the formation of novel varieties and entire new species. These changes are responsible for the diverse forms of life inhabiting the planet. The evidence for evolution suggests that all living organisms descended from common ancestors.
48.1K
Convergent Evolution
32.9K
Evolution shapes the features of organisms over time, ensuring that they are suited for the environments in which they live. Sometimes, selection pressure leads to the rise of similar but unrelated adaptations in organisms with no recent common ancestors, a process known as convergent evolution.
32.9K
Initiation of Translation
39.0K
Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
39.0K
Initiation of Translation
8.1K
8.1K
pH Scale
79.7K
Hydronium and hydroxide ions are present both in pure water and in all aqueous solutions, and their concentrations are inversely proportional as determined by the ion product of water (Kw). The concentrations of these ions in a solution are often critical determinants of the solution’s properties and the chemical behaviors of its other solutes. Two different solutions can differ in their hydronium or hydroxide ion concentrations by a million, billion, or even trillion times. A common means of...
79.7K
Eukaryotic Evolution
41.4K
The endosymbiont theory is the most widely accepted theory of eukaryotic evolution; however, its progression is still somewhat debated. According to the nucleus-first hypothesis, the ancestral prokaryote first evolved a membrane to enclose DNA and form the nucleus. Conversely, the mitochondria-first hypothesis suggests that the nucleus was formed after endosymbiosis of mitochondria.
Contrary to the endosymbiont theory, the eukaryote-first hypothesis proposes that the simpler prokaryotic and...
Contrary to the endosymbiont theory, the eukaryote-first hypothesis proposes that the simpler prokaryotic and...
41.4K
