在单细胞分辨率下绘制HLA基因的动态遗传调节结构
Joyce B Kang1,2,3,4,5, Amber Z Shen1,2,3,4,5, Saisriram Gurajala1,2,3,4,5
1Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.
Nature genetics
|November 30, 2023
概括
这项研究揭示了遗传变异如何影响不同细胞类型的人类白细胞抗原 (HLA) 基因表达. 这些HLA基因的动态表达变化对于理解免疫反应变异性至关重要.
科学领域:
- 免疫遗传学 免疫遗传学
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 人类白细胞抗原 (HLA) 位对免疫功能至关重要,包括疾病易感性和移植.
- 虽然HLA基因的编码变异已得到充分研究,但影响它们表达的调节变异仍未得到充分研究.
研究的目的:
- 在单细胞分辨率下为经典HLA基因绘制表达量的特征位点 (eQTLs).
- 研究影响HLA表达的细胞类型特定和细胞状态依赖的调节性遗传变异.
主要方法:
- 开发了scHLApers,使用个性化参考基因组精确量化单细胞HLA表达的管道.
- 在1,073个个体和来自三个组织的100多万个单细胞中绘制了经典HLA基因的cis-eQTL.
主要成果:
- 确定了所有经典HLA基因的细胞类型特定的cis-eQTL.
- 证明了动态的,细胞状态依赖的eQTL效应,特别是在髓状细胞,B细胞和T细胞中的HLA-DQ基因.
- 展示了一种特定的T细胞HLA-DQA1 eQTL (rs3104371) 在细胞毒性细胞中具有最强效应.
结论:
- 单细胞分辨率揭示了HLA基因表达的动态调节.
- 动态HLA调节对免疫反应的个体间差异作出了重大贡献.
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