Spatial epigenome-transcriptome co-profiling of mammalian tissues.
Spatial epigenome-transcriptome co-profiling of mammalian tissues.
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哺乳动物组织的空间表观基因组-转录组共谱。
DOI：
10.1038/s41586-023-05795-1
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发表时间：
2023-04
期刊：
影响因子：
64.8
通讯作者：
Fan, Rong
中科院分区：
文献类型：
--
作者：
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, Goncalo;Fan, Rong
新兴的空间技术，包括空间转录组学和空间表观基因组学，正在成为在组织背景下分析细胞状态的强大工具。然而，目前的方法一次只能捕获一层组学信息，排除了检查分子生物学中心法则之间的机制关系的可能性。在这里，我们提出了两种技术的空间分辨，全基因组，联合分析的表观基因组和转录组共测序染色质的可及性和基因表达，或组蛋白修饰（H3K27me3，H3K27ac或H3K4me3）和基因表达在同一组织切片在近单细胞分辨率。这些被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，但我们也观察到了不同的模式，表明它们在定义细胞状态中的不同作用。通过将表观基因组与转录组像素连接，可以揭示组织结构中空间表观遗传启动、分化和基因调控的新见解。这些技术在生命科学和生物医学研究中具有重要意义。作者提出了两种技术，用于空间分辨的，全基因组的，表观基因组和转录组的联合分析，通过共测序染色质可及性和基因表达，或组蛋白修饰和基因表达在同一组织切片上，在近单细胞分辨率。
Emerging spatial technologies, including spatial transcriptomics and spatial epigenomics, are becoming powerful tools for profiling of cellular states in the tissue context. 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. The authors 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 and gene expression on the same tissue section at near-single-cell resolution.
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影响因子：
64.8
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通讯作者：
Shendure, Jay
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64.5
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Fan R