并非所有对照都是平等的:通过单细胞基因表达特征来定义人类基因参考样本
medRxiv : the preprint server for health sciences
|April 1, 2025
概括
参考组织样本类型对研究结果产生重大影响. 对采购方法和捐赠者的年龄进行核算对于准确识别病机制至关重要.
科学领域:
- 病理学和分子生物学
- 单细胞基因组学和转录基因组学
- 在病中发现生物标志物
背景情况:
- 识别病机制依赖于将患病的组织与健康参考进行比较.
- 样本采购,储存和供体特征对参考组织的影响不明.
- 参考样本的变化可能会混差异性基因表达分析.
研究的目的:
- 为了评估三种不同的基准样本类型的完整性和损伤生物标志物.
- 评估参考样本变异对在糖尿病病 (DKD) 中识别差异表达基因 (DEGs) 的影响.
- 在分子分析中开发控制年龄和组织采购效应的工具.
主要方法:
- 分析来自三个参考组织类型的单细胞基因表达特征:瘤腎切除术 (TN),活体供体活检 (LD) 和健康对照活检 (HC).
- 评估损伤/疾病标志物和细胞状态比例.
- 鉴定与采购效应和与年龄相关的转录特征相关的基因组.
主要成果:
- 在TN,LD和HC样本中观察到不同的转录形状,受采购方法和年龄的影响.
- 与LD相比,TN样本显示压力反应基因和潜在病理的表达更高.
- 鉴定了采购和年龄相关的基因组,影响了DKD比较中的DEG分析.
结论:
- 参考样品类型对分子分析和疾病关联研究产生了重大影响.
- 考虑到年龄和组织采购效应对于准确解释DEGs对于像DKD这样的脏疾病至关重要.
- 标准化的参考样本选择和数据规范化对于对病态的稳健分子评估至关重要.
相关概念视频
01:58Cell Specific Gene Expression
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
01:58Cell Specific Gene Expression
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...