小柯机器人

近日，美国斯坦福大学的Jonathan K. Pritchard、William J. Greenleaf以及加州大学旧金山分校的Alexander Marson、Lindsey A. Criswell等研究人员合作描绘了不同人类免疫细胞的刺激响应染色质图谱。相关论文于2019年9月30日在线发表于国际学术期刊《自然—遗传学》。

研究人员在静息和刺激条件下，针对多达32个免疫细胞群，使用测序（ATAC-seq）和RNA测序数据获得了转座酶及染色质分析。刺激引起广泛的染色质重塑，包括刺激的B细胞和T细胞之间共有的响应元件。此外，几种自身免疫性状在来自不同细胞类型的刺激应答元件中显示出显著的遗传力，从而突显了这些细胞状态在自身免疫中的重要性。等位基因特异性阅读图谱鉴定了在特定条件下会改变染色质可及性的变体，这使研究人员能够观察到候选因果变体的功能证据，而静息细胞中的现有大规模研究并未发现这种变体。这些结果提供了染色质动态的资源，并强调了表征受刺激细胞中遗传变异影响的必要性。

据悉，免疫系统的标志是在静息和刺激状态之间特定细胞类型转换之间的相互作用。这种动态系统的基因调控图谱尚未在人类细胞中得到充分表征。

附：英文原文

Title: Landscape of stimulation-responsive chromatin across diverse human immune cells

Author: Diego Calderon, Michelle L. T. Nguyen, Anja Mezger, Arwa Kathiria, Fabian Mller, Vinh Nguyen, Ninnia Lescano, Beijing Wu, John Trombetta, Jessica V. Ribado, David A. Knowles, Ziyue Gao, Franziska Blaeschke, Audrey V. Parent, Trevor D. Burt, Mark S. Anderson, Lindsey A. Criswell, William J. Greenleaf, Alexander Marson, Jonathan K. Pritchard

Issue&Volume: 2019-09-30

Abstract: A hallmark of the immune system is the interplay among specialized cell types transitioning between resting and stimulated states. The gene regulatory landscape of this dynamic system has not been fully characterized in human cells. Here we collected assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA sequencing data under resting and stimulated conditions for up to 32 immune cell populations. Stimulation caused widespread chromatin remodeling, including response elements shared between stimulated B and T cells. Furthermore, several autoimmune traits showed significant heritability in stimulation-responsive elements from distinct cell types, highlighting the importance of these cell states in autoimmunity. Allele-specific read mapping identified variants that alter chromatin accessibility in particular conditions, allowing us to observe evidence of function for a candidate causal variant that is undetected by existing large-scale studies in resting cells. Our results provide a resource of chromatin dynamics and highlight the need to characterize the effects of genetic variation in stimulated cells. 

DOI: 10.1038/s41588-019-0505-9

Source:https://www.nature.com/articles/s41588-019-0505-9

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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