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C/EBPβ依赖的表观遗传对造血干细胞免疫的影响
作者:小柯机器人 发布时间:2020/3/23 13:58:43

法国艾克斯-马赛大学Michael H. Sieweke和Sandrine Sarrazin研究团队宣布他们发现C /EBPβ依赖的表观遗传记忆诱导造血干细胞(HSC)的后天免疫。2020年3月12日出版的《细胞-干细胞》杂志在线发表了这项成果。

研究人员发现脂多糖(LPS)的急性免疫刺激仅诱导HSC丰度、组成、子代和基因表达的瞬时变化,但同时也发生了特定髓系谱系增强子可及性的持续变化,这增强了相关免疫基因对继发刺激的反应。在功能上,这与先前暴露HSC的骨髓生成增加和对铜绿假单胞菌(革兰氏阴性菌)的先天免疫力有关。

可及的骨髓样增强子富含C /EBPβ(靶标)并且C /EBPβ的缺失消除了LPS诱导的表观遗传标记和基因持续表达。因此,短暂免疫信号传导可以诱导C /EBPβ依赖的染色质可及性,在继发感染期间产生受HSC诱导的免疫。该研究揭示了一种机制,即感染史如何通过表观遗传转化为HSC中固有免疫的整体记忆。

据了解,HSC可以维持免疫细胞的终生生产,并且可以直接对感染作出反应,但是HSC对免疫反应的持续影响仍然不清楚。

附:英文原文

Title: C/EBPβ-Dependent Epigenetic Memory Induces Trained Immunity in Hematopoietic Stem Cells

Author: Bérengère de Laval, Julien Maurizio, Prashanth K. Kandalla, Gabriel Brisou, Louise Simonnet, Caroline Huber, Gregory Gimenez, Orit Matcovitch-Natan, Susanne Reinhardt, Eyal David, Alexander Mildner, Achim Leutz, Bertrand Nadel, Christophe Bordi, Ido Amit, Sandrine Sarrazin, Michael H. Sieweke

Issue&Volume: 2020-03-12

Abstract: Hematopoietic stem cells (HSCs) maintain life-long production of immune cells andcan directly respond to infection, but sustained effects on the immune response remainunclear. We show that acute immune stimulation with lipopolysaccharide (LPS) inducedonly transient changes in HSC abundance, composition, progeny, and gene expression,but persistent alterations in accessibility of specific myeloid lineage enhancersoccurred, which increased responsiveness of associated immune genes to secondary stimulation.Functionally, this was associated with increased myelopoiesis of pre-exposed HSC andimproved innate immunity against the gram-negative bacterium P. aeruginosa. The accessible myeloid enhancers were enriched for C/EBPβ (targets, and C/EBPβ deletionerased the long-term inscription of LPS-induced epigenetic marks and gene expression.Thus, short-term immune signaling can induce C/EBPβ-dependent chromatin accessibility,resulting in HSC-trained immunity, during secondary infection. This establishes amechanism for how infection history can be epigenetically inscribed in HSC as an integralmemory function of innate immunity.

DOI: 10.1016/j.stem.2020.01.017

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30017-5

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx