细胞循环合的转录网络编排人类B细胞命运分支
Nicholas A Pease1, Jingyu Fan1, Swapnil Keshari1,2
1Center for Systems Immunology and Departments of Immunology and Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA.
bioRxiv : the preprint server for biology
|July 16, 2025
概括
研究人员绘制了控制人类B细胞命运的基因调节网络. 确定了像IRF4和BLIMP1这样的关键转录因子,揭示了反循环,这些反循环决定了等离子细胞和生殖中心B细胞分化.
科学领域:
- 免疫学 免疫学 免疫学
- 系统生物学 系统生物学
- 遗传学 遗传学 是一个
背景情况:
- 抗体的产生依赖于B细胞分化成等离子细胞 (PBs) 和生殖中心B细胞 (GCBCs).
- 控制这种人类B细胞命运决定的基因调节网络 (GRNs) 尚未完全理解.
研究的目的:
- 阐明控制人类B细胞命运选择向PB和GCBC分化方向的高分辨率GRNs.
- 确定关键的转录因子 (TF) 和参与B细胞分支的调控机制.
主要方法:
- 利用暂时解决的单细胞多组学.
- 采用计算建模和基于CRISPR的扰动来组装,模拟和测试GRN.
- 在单核酸分辨率下分析了转录因子结合和作用.
主要成果:
- 组装和验证的高分辨率GRNs用于PB和GC fates.
- 确定了IRF4及其在IRF的合作伙伴的主导,互惠的行动.
- 发现了涉及TFs控制B细胞分支的相互负反循环.
- 显示IRF4和BLIMP1共同抑制细胞周期基因MYC和CCND2.2.
- 发现了一个调控模块,将细胞周期动态 (G0/G1延长) 与增强的PB规范联系起来.
结论:
- 通过负反循环,IRF4和BLIMP1在B细胞命运决定中发挥着关键作用.
- 细胞周期调节与B细胞命运选择相结合,促进了等离子体细胞的分化.
- 这项研究提供了一个关于人类B细胞命运决定的GRNs的综合模型.
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