Essential contributions of enhancer genomic regulatory elements to microglial cell identity and functions.

IF 7.9 Q1 Medicine Wiley Interdisciplinary Reviews-Systems Biology and Medicine Pub Date : 2019-09-01 Epub Date: 2019-04-23 DOI:10.1002/wsbm.1449
André Machado Xavier, Sarah Belhocine, David Gosselin
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引用次数: 1

Abstract

Microglia are the specialized macrophages of the brain and play essential roles in ensuring its proper functioning. Accumulating evidence suggests that these cells coordinate the inflammatory response that accompanies various clinical brain conditions, including neurodegenerative diseases and psychiatric disorders. Therefore, investigating the functions of these cells and how these are regulated have become important areas of research in neuroscience over the past decade. In this regards, recent efforts to characterize the epigenomic mechanisms underlying microglial gene transcription have provided significant insights into the mechanisms that control the ontogeny and the cellular competences of microglia. In particular, these studies have established that a substantial proportion of the microglial repertoire of promoter-distal genomic regulatory elements, or enhancers, is relatively specific to these cells compared to other tissue-resident macrophages. Notably, this specificity is under the regulation of factors present in the brain that modulate activity of target axes of signaling pathways-transcription factors in microglia. Thus, the microglial enhancer repertoire is highly responsive to perturbations in the cerebral tissue microenvironment and this responsiveness has profound implications on the activity of these cells in brain diseases. This article is categorized under: Physiology > Mammalian Physiology in Health and Disease Models of Systems Properties and Processes > Mechanistic Models Biological Mechanisms > Cell Fates Developmental Biology > Lineages.

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增强基因组调控元件对小胶质细胞身份和功能的重要贡献。
小胶质细胞是大脑中特化的巨噬细胞,在确保大脑正常运作中起着至关重要的作用。越来越多的证据表明,这些细胞协调伴随各种临床脑疾病的炎症反应,包括神经退行性疾病和精神疾病。因此,在过去的十年中,研究这些细胞的功能以及它们是如何被调节的已经成为神经科学研究的重要领域。在这方面,最近表征小胶质细胞基因转录的表观基因组机制的努力为控制小胶质细胞的个体发生和细胞能力的机制提供了重要的见解。特别是,这些研究已经确定,与其他组织驻留巨噬细胞相比,启动子-远端基因组调控元件或增强子的相当大比例的小胶质细胞库对这些细胞相对特异性。值得注意的是,这种特异性是在大脑中存在的调节信号通路靶轴活动的因子-小胶质细胞中的转录因子的调节下产生的。因此,小胶质增强子库对脑组织微环境的扰动具有高度反应性,这种反应性对脑疾病中这些细胞的活动具有深远的影响。本文分类如下:生理学>健康和疾病中的哺乳动物生理学系统特性和过程模型>机制模型生物学机制>细胞命运发育生物学>谱系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
18.40
自引率
0.00%
发文量
0
审稿时长
>12 weeks
期刊介绍: Journal Name:Wiley Interdisciplinary Reviews-Systems Biology and Medicine Focus: Strong interdisciplinary focus Serves as an encyclopedic reference for systems biology research Conceptual Framework: Systems biology asserts the study of organisms as hierarchical systems or networks Individual biological components interact in complex ways within these systems Article Coverage: Discusses biology, methods, and models Spans systems from a few molecules to whole species Topical Coverage: Developmental Biology Physiology Biological Mechanisms Models of Systems, Properties, and Processes Laboratory Methods and Technologies Translational, Genomic, and Systems Medicine
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