학술논문

Spatial epigenome–transcriptome co-profiling of mammalian tissues
Document Type
article
Source
Nature. 616(7955)
Subject
Genetics
Biotechnology
Human Genome
Rare Diseases
Underpinning research
1.1 Normal biological development and functioning
Generic health relevance
Animals
Humans
Mice
Chromatin
Epigenesis
Genetic
Epigenome
Epigenomics
Gene Expression Profiling
Gene Expression Regulation
Mammals
Transcriptome
Histones
Single-Cell Analysis
Organ Specificity
Brain
Aging
General Science & Technology
Language
Abstract
Emerging spatial technologies, including spatial transcriptomics and spatial epigenomics, are becoming powerful tools for profiling of cellular states in the tissue context1-5. 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.