伪基SsCLEC9A的单细胞转录足迹与Sus scrofa中的抗原处理和呈现有关
Xiaoyang Yang1, Shaojun Yang2, Yabiao Luo1
1Department of Animal Genetics and Breeding, National Engineering Laboratory for Animal Breeding, MOA Key Laboratory of Animal Genetics and Breeding, Beijing Key Laboratory for Animal Genetic Improvement, State Key Laboratory of Animal Biotech Breeding, Frontiers Science Center for Molecular Design Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
International journal of biological macromolecules
|February 4, 2025
概括
由于古老的突变,猪具有非功能性CLEC9A基因,影响免疫交叉呈现. 这种伪基因.
科学领域:
- 免疫学 免疫学 免疫学
- 遗传学 遗传学 是一个
- 进行比较基因组学.
背景情况:
- C型莱克域家族9成员A (CLEC9A) 对于树突细胞 (DC) 中的抗原交叉呈现至关重要.
- 不同哺乳动物物种在免疫反应中CLEC9A的作用尚未完全理解.
- 伪基因化,即基因的失活,可以提供对进化适应和免疫功能的见解.
研究的目的:
- 为了研究猪中CLEC9A基因的功能状态.
- 了解CLEC9A伪基化对免疫细胞功能和抗原呈现的影响.
- 探索恢复CLEC9A功能以增强猪免疫力的潜在策略.
主要方法:
- 生物信息分析以确定猪CLEC9A基因 (SsCLEC9A) 中的突变.
- 光激活细胞分类 (FACS) 和单细胞RNA测序 (scRNA-seq) 用于分析猪DC中的基因表达.
- 功能性测试涉及基因编辑和抗原处理和呈现途径的评估.
主要成果:
- 唯一的猪CLEC9A基因 (SsCLEC9A) 是一个伪基因,大约在29.8-44.7百万年前被三个突变无活化.
- 一个突变的SsCLEC9A转录被转录并主要以DCs表达,与CLEC7A表达相关联.
- 表达突变SsCLEC9A转录的猪DCs显示细胞相互作用和抗原呈现减少,类似于成熟的DCs.
- 在造血细胞中恢复保存的CLEC9A序列增强了抗原处理和呈现基因表达.
结论:
- 猪中CLEC9A的伪基化挑战了它在哺乳动物免疫交叉呈现中的普遍重要性.
- 该研究建立了一个自然伪基因模型来研究转录适应及其对免疫功能的影响.
- 这些发现为未来的研究提供了基础,旨在挽救SsCLEC9A功能以改善猪免疫力.
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