集成的单细胞转录学揭示了NASH衍生的肝细胞癌中缺氧诱导的炎症癌变
Yuan Liang1,2, Rui Zhang1, Siddhartha Biswas1
1Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing Medical University, Nanjing, China.
Cell proliferation
|November 23, 2023
概括
非酒精性脂肪肝 (NAFLD) 驱动肝癌 (HCC) 通过过渡性肝细胞和缺氧. 缺氧促进免疫抑制性巨细胞,帮助NAFLD相关的HCC进展,并提供新的治疗点.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
背景情况:
- 非酒精性脂肪肝 (NAFLD) 是由于代谢综合征导致的肝癌 (HCC) 的主要原因.
- 免疫细胞和恶性肝细胞转化在NAFLD相关的HCC中的作用尚未完全理解.
研究的目的:
- 阐明与NAFLD相关的HCC发展背后的细胞和分子机制.
- 确定参与肝细胞恶性转化和免疫微环境调节的关键细胞参与者和途径.
主要方法:
- 从健康和NAFLD肝脏组织中分析单细胞转录组数据.
- 进行了差异组合,功能丰富,伪时间和SCENIC分析.
- 使用非酒精性脂肪肝炎 (NASH) 的小鼠模型验证HCC转化.
主要成果:
- 在癌前病变中确定了CYP7A1+"过渡细胞",表现出压力,炎症和癌症途径.
- 证明肝细胞中缺氧激活 (HIF1A),促进增殖和血管生成.
- 通过CCL15-CCR1轴揭示了免疫抑制TREM2+巨细胞的缺氧诱导的两极分化,增强了瘤的进展.
结论:
- 与NAFLD相关的HCC涉及过渡性肝细胞和缺氧驱动的免疫抑制微环境.
- 肝细胞衍生的缺氧和巨细胞两极分化在NAFLD-HCC的发病过程中至关重要.
- 这些发现支持NAFLD相关的肝癌的新型治疗点.
相关概念视频
02:53Adaptive Mechanisms in Cancer Cells
5.8K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.8K
02:39lncRNA - Long Non-coding RNAs
8.6K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.6K