使用人肝芯片模型开发用于辐射损伤的RNA签名
Shannon Martello1, Yuki Ueda1, Michelle A Bylicky1
1Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Radiation research
|August 1, 2024
概括
一个人肝芯片模型确定了辐射诱导肝损伤 (RILI) 的生物标志物. 这个模型有助于开发医疗对策和理解辐射.
科学领域:
- 生物医学工程 生物医学工程
- 毒理学 毒理学 毒理学
- 基因组学就是基因组学.
背景情况:
- 暴露于辐射需要改进医疗分类和对抗措施以求生存.
- 辐射诱导性肝损伤 (RILI) 缺乏早期诊断测试,动物模型不能完全复制人类的反应.
- 确定RILI的生物标志物对于及时干预和治疗至关重要.
研究的目的:
- 建立一个人肝芯片模型,用于研究辐射诱导的组织损伤.
- 为了确定RNA表达和生物通路的急性变化,表明RILI.
- 发现RILI的潜在生物标志物和机制,用于医学对策的开发.
主要方法:
- 在微流体肝芯片系统中共同培养人类肝脏鼻状内皮细胞 (LSEC) 和肝细胞.
- 用0 Gy,1 Gy,4 Gy或10 Gy对芯片进行辐射,然后在6小时,24小时和7天内进行细胞采集.
- 使用RNA测序 (RNASeq) 进行全转录组分析,以识别差异表达的信使RNA (mRNA) 和长非编码RNA (lncRNA).
主要成果:
- 根据辐射剂量,时间和细胞类型 (LSEC 与肝细胞) 观察到RNA表达模式的明显差异.
- 较高的辐射剂量导致更明显的表达变化;细胞活力途径在LSEC和肝细胞中显示出差异性反应.
- 发现的关键的潜在生物标志物包括APOBEC3H,PTCHD4,GDNF,DINO,PURPL,TMPO-AS1和PRC-AS1.
结论:
- 一个人肝芯片模型有效模拟器官特定的辐射损伤,验证了它对研究的有用性.
- 该研究确定了新型生物标志物,这些生物标志物可以区分辐射剂量和辐射缓解疗法的细胞特异性标.
- 该模型为开发和验证辐射医学对策提供了一个平台.
相关概念视频
01:23RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
01:23RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...