改变的AP-1,RUNX和EGR染色体动态驱动纤维性肺病
Eleanor Valenzi1,2, Minxue Jia3, Peter Gerges4
1Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Pittsburgh.
bioRxiv : the preprint server for biology
|November 18, 2024
概括
研究人员确定了驱动肺纤维化中纤维化的关键转录因子 (TF),特别是与系统性硬化症相关的间歇性肺病 (SSc-ILD). 这本TF行动图谱揭示了控制肺细胞中益纤维菌基因程序的调控网络.
科学领域:
- 肺部医学 肺部医学
- 细胞和分子生物学是细胞和分子生物学.
- 基因组学和生物信息学
背景情况:
- 肺纤维化,包括系统性硬化症相关的间歇性肺病 (SSc-ILD),是由肌纤维细胞和特定的巨细胞群驱动的.
- 虽然已知转录组,但profibrotic基因程序的转录控制机制仍然不清楚.
研究的目的:
- 阐明在健康和SSc-ILD人类肺部中的纤维细胞和巨细胞中控制益菌菌基因表达的转录调节网络.
主要方法:
- 多原子单核测试用于转化酶可访问的染色体测序 (snATAC-seq) 和单核RNA测序 (snRNA-seq) 在已扩展的SSc-ILD和供体对照肺部进行.
- 使用神经网络工具ChromBPNet分析了染色质可访问性数据,以推断转录因子 (TF) 的结合.
- 一种新的算法HALO被用来识别活跃的TF,并构建TF调节元素-基因网络.
主要成果:
- 克罗姆BPNet确定了SSc-ILD纤维细胞中的CTHRC1和ADAM12,以及巨细胞中的SPP1和CCL18等益纤维细胞基因的TF结合增加.
- 哈洛证实了AP-1,RUNX和EGRTFs在控制益菌性基因程序中的活性.
- 建立了全面的TF调节元素-基因网络,详细介绍了肺细胞中的转录控制.
结论:
- 这项研究介绍了一本TF行动图谱,深入了解肺纤维化中纤维细胞和巨细胞的转录调节.
- 这些发现突出了特定的TF和监管网络,这些网络对于SSc-ILD中益菌性基因表达至关重要.
- 这项工作为理解和潜在地针对肺部纤维化通路提供了基础.
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