转录因子活动 调节巨细胞在皮肤伤口愈合过程中的异质性
Mehrdad Zandigohar1, Jingbo Pang2, Alannah Rodrigues1
1Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, IL.
Journal of immunology (Baltimore, Md. : 1950)
|June 28, 2024
概括
单细胞和巨细胞 (Mos/Mφs) 在伤口愈合中的异质性是由转录因子 (TF) 活动调节的. NR4A1 TF活性促进炎症并损害皮肤伤口愈合.
科学领域:
- 免疫学 免疫学 免疫学
- 伤口愈合 治愈 伤口愈合
- 计算生物学 计算生物学
背景情况:
- 单细胞和巨细胞 (Mos/Mφs) 呈现出各种功能表型,这些表型对于伤口愈合至关重要.
- 在皮肤修复过程中管理Mo/Mφ异质性的调节机制尚不清楚.
研究的目的:
- 通过使用增强的贝叶斯推断模型,推断皮肤伤口愈合期间Mos/Mφs中的转录因子 (TF) 活性.
- 研究特定TFs,如NR4A1在调节Mo/Mφ表型和伤口愈合结果中的作用.
主要方法:
- 单细胞RNA测序和单细胞ATAC测序数据的整合.
- 贝叶斯推理建模来预测TF活动.
- 网络分析以确定TF社区和合作.
- 使用 Nr4a1 淘汰赛小鼠模型进行验证.
主要成果:
- 伤口Mos/Mφs被分为不同的集群,具有差异性的染色质可访问性和TF活性.
- TF网络分析揭示了合作的TF,并确定了与炎症相关的NR4A1/NFKB1社区.
- 验证了NR4A1的活性是促炎的,Nr4a1淘汰的小鼠显示炎症减少和伤口愈合受损.
结论:
- 这项研究阐明了调节伤口愈合中的Mo/Mφ异质性的TF活性.
- 这些发现为针对Mo/Mφ TF网络提供了基础,以调节细胞表型并增强愈合.
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