系统地识别基因组合以准天生的免疫细胞,以增强T细胞激活
Lei Xia1, Anastasia Komissarova1, Arielle Jacover1
1The Lautenberg Center for Immunology and Cancer Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 91120, Israel.
Nature communications
|October 9, 2023
概括
这项研究使用高多重性乱和转录体和表皮体的细胞索引 (HMPCITE-seq) 来识别增强免疫细胞活性的基因组合. 针对Cebpb和Med12一起,比单基因点更能改善抗原呈现细胞功能.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 免疫细胞的基因工程为增强功能提供了潜力.
- 确定免疫细胞改善的最佳基因标仍然是一个挑战.
研究的目的:
- 发现改善抗原呈现细胞 (APC) 活动和T细胞激活的基因组合.
- 为了利用全基因组的CRISPR屏幕和高阶的Perturb-Seq进行基因相互作用分析.
主要方法:
- 在骨髓树状细胞上进行了全基因组的CRISPR选.
- 使用了高多重性乱和转录体和表皮体 (HMPCITE-seq) 的细胞索引.
- 高级 Perturb-Seq 实验发现了遗传相互作用.
主要成果:
- 确定了CD86 (共刺激) 的负调节剂和PD-L1 (共抑制) 的正调节剂.
- 涉及的基因包括Chd4,Stat5b,Egr2,Med12,Sptlc2,Nckap1l和Pi4kb等基因.这些基因都被认为是相关的.
- 与单个干扰相比,Cebpb和Med12的联合向表明了优越的表型.
结论:
- 该研究成功地确定了增强APC功能的基因组合.
- 针对特定的基因对,如Cebpb和Med12,可以协同改善免疫细胞介导的T细胞激活.
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