Ludwig Institute for Cancer Research, La Jolla, CA, USA.
Department of Cellular and Molecular Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA.
Nat Methods. 2021 Mar;18(3):283-292. doi: 10.1038/s41592-021-01060-3. Epub 2021 Feb 15.
Genome-wide profiling of histone modifications can reveal not only the location and activity state of regulatory elements, but also the regulatory mechanisms involved in cell-type-specific gene expression during development and disease pathology. Conventional assays to profile histone modifications in bulk tissues lack single-cell resolution. Here we describe an ultra-high-throughput method, Paired-Tag, for joint profiling of histone modifications and transcriptome in single cells to produce cell-type-resolved maps of chromatin state and transcriptome in complex tissues. We used this method to profile five histone modifications jointly with transcriptome in the adult mouse frontal cortex and hippocampus. Integrative analysis of the resulting maps identified distinct groups of genes subject to divergent epigenetic regulatory mechanisms. Our single-cell multiomics approach enables comprehensive analysis of chromatin state and gene regulation in complex tissues and characterization of gene regulatory programs in the constituent cell types.
全基因组组蛋白修饰谱分析不仅可以揭示调控元件的位置和活性状态，还可以揭示发育过程中和疾病病理过程中细胞类型特异性基因表达的调控机制。对批量组织中组蛋白修饰进行分析的传统方法缺乏单细胞分辨率。在这里，我们描述了一种超高通量的方法 Paired-Tag，用于在单细胞中联合分析组蛋白修饰和转录组，以生成复杂组织中染色质状态和转录组的细胞类型分辨图谱。我们使用这种方法在成年小鼠大脑皮层和海马体中联合分析了五个组蛋白修饰和转录组。对生成图谱的综合分析确定了受不同表观遗传调控机制影响的不同基因群。我们的单细胞多组学方法能够全面分析复杂组织中的染色质状态和基因调控，并对组成细胞类型中的基因调控程序进行特征描述。
