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哺乳动物组织的空间表观基因组和转录组联合分析
2023-03-23 11:42

美国耶鲁大学Rong Fan、瑞典卡罗林斯卡医学院Gonçalo Castelo-Branco和美国宾夕法尼亚大学Yanxiang Deng共同合作,近期取得重要工作进展。他们对哺乳动物组织的空间表观基因组和转录组进行了联合分析。相关研究成果2023年3月15日在线发表于《自然》杂志上。

据介绍,新兴的空间组学技术(包括空间转录组学和空间表观基因组学),正在成为在组织环境中分析细胞状态的强大工具。然而,目前的方法一次只捕获一层组学信息,排除了通过分子生物学的中心法则来研究机制关系的可能性。

研究人员提出了两种技术,通过染色质可及性和基因表达的共测序,以及组蛋白修饰(H3K27me3、H3K27ac或H3K4me3)和基因在同一组织切片上的基因表达,实现空间分辨率,全基因组,表观基因组和转录组的联合分析,以接近单细胞分辨率。这些应用于胚胎和幼年小鼠大脑以及成年人脑,以绘制表观遗传学机制如何控制组织中的转录表型和细胞动力学。尽管通过空间表观基因组或空间转录组鉴定了高度一致的组织特征,但研究人员也观察到了不同的模式,这表明它们在定义细胞状态中的不同作用。将表观基因组与转录组逐像素连接,可以揭示组织结构中空间表观遗传学启动、分化和基因调控方面的新见解。

总之,这些技术在生命科学和生物医学研究中具有重要的意义。

附:英文原文

Title: Spatial epigenome–transcriptome co-profiling of mammalian tissues

Author: Zhang, Di, Deng, Yanxiang, Kukanja, Petra, Agirre, Eneritz, Bartosovic, Marek, Dong, Mingze, Ma, Cong, Ma, Sai, Su, Graham, Bao, Shuozhen, Liu, Yang, Xiao, Yang, Rosoklija, Gorazd B., Dwork, Andrew J., Mann, J. John, Leong, Kam W., Boldrini, Maura, Wang, Liya, Haeussler, Maximilian, Raphael, Benjamin J., Kluger, Yuval, Castelo-Branco, Gonalo, Fan, Rong

Issue&Volume: 2023-03-15

Abstract: Emerging spatial technologies, including spatial transcriptomics and spatial epigenomics, are becoming powerful tools for profiling of cellular states in the tissue context1,2,3,4,5. However, current methods capture only one layer of omics information at a time, precluding the possibility of examining the mechanistic relationship across the central dogma of molecular biology. Here, we present two technologies for spatially resolved, genome-wide, joint profiling of the epigenome and transcriptome by cosequencing chromatin accessibility and gene expression, or histone modifications (H3K27me3, H3K27ac or H3K4me3) and gene expression on the same tissue section at near-single-cell resolution. These were applied to embryonic and juvenile mouse brain, as well as adult human brain, to map how epigenetic mechanisms control transcriptional phenotype and cell dynamics in tissue. Although highly concordant tissue features were identified by either spatial epigenome or spatial transcriptome we also observed distinct patterns, suggesting their differential roles in defining cell states. Linking epigenome to transcriptome pixel by pixel allows the uncovering of new insights in spatial epigenetic priming, differentiation and gene regulation within the tissue architecture. These technologies are of great interest in life science and biomedical research.

DOI: 10.1038/s41586-023-05795-1

Source: https://www.nature.com/articles/s41586-023-05795-1

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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