环境驱动增强剂的选择和功能,控制特定组织的巨细胞身份
David Gosselin1, Verena M Link2, Casey E Romanoski1
1Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0651, USA.
Cell
|December 7, 2014
概括
组织环境通过改变基因表达来塑造巨细胞的功能. 研究人员确定了特定的转录因子和增强剂如何合作,在不同的组织中产生独特的巨细胞表型,影响免疫反应和平衡.
科学领域:
- 免疫学和细胞生物学
- 基因组学和转录基因组学
- 组织恒常机制 组织恒常机制
背景情况:
- 巨细胞是所有组织中发现的关键免疫细胞,在先天性和适应性免疫中起着至关重要的作用.
- 专门的组织巨细胞群体表现出维护组织健康和恒常性至关重要的独特功能.
- 了解组织特异性巨细胞功能的分子基础对于促进免疫学和再生医学的发展至关重要.
研究的目的:
- 研究驱动巨细胞中特定组织功能的分子机制,重点关注大脑微质细胞和腹巨细胞.
- 识别转录因子和调控元素 (增强剂),这些因素决定了巨细胞子集特定的基因表达程序.
- 为了阐明不同的组织环境如何通过差异性基因调节影响巨细胞表型.
主要方法:
- 对大脑微质细胞和腹膜巨细胞进行比较的转录组分析.
- 在不同的巨细胞群体中绘制增强器景观的映射.
- 利用自然遗传变异作为全基因组突变发生的方法来识别PU.1.的转录因子结合基因.
主要成果:
- 不同的组织环境在巨细胞中诱导不同的基因表达程序.
- 一个共同的增强剂谱的差异激活和二次转录因子的诱导有助于组织特定的表型.
- 鉴定调节PU.1结合的转录因子的DNA识别动机,以情境依赖的方式.
结论:
- 组织微环境在塑造巨细胞功能性身份方面发挥着关键作用.
- 共有和分歧的调节机制的组合,涉及增强剂和转录因子,建立组织特异性的巨细胞表型.
- 这些发现为细胞可塑性提供了洞察力,并对理解巨细胞以外的细胞类型特定基因调节有广泛的影响.
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