单细胞在复杂组织中的空间分辨表观基因组分析。
Spatially resolved epigenomic profiling of single cells in complex tissues.
机构信息
Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Department of Physics, Harvard University, Cambridge, MA 02138, USA.
Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Department of Physics, Harvard University, Cambridge, MA 02138, USA.
出版信息
Cell. 2022 Nov 10;185(23):4448-4464.e17. doi: 10.1016/j.cell.2022.09.035. Epub 2022 Oct 21.
The recent development of spatial omics methods has enabled single-cell profiling of the transcriptome and 3D genome organization with high spatial resolution. Expanding the repertoire of spatial omics tools, a spatially resolved single-cell epigenomics method will accelerate understanding of the spatial regulation of cell and tissue functions. Here, we report a method for spatially resolved epigenomic profiling of single cells using in situ tagmentation and transcription followed by multiplexed imaging. We demonstrated the ability to profile histone modifications marking active promoters, putative enhancers, and silent promoters in individual cells, and generated high-resolution spatial atlas of hundreds of active promoters and putative enhancers in embryonic and adult mouse brains. Our results suggested putative promoter-enhancer pairs and enhancer hubs regulating developmentally important genes. We envision this approach will be generally applicable to spatial profiling of epigenetic modifications and DNA-binding proteins, advancing our understanding of how gene expression is spatiotemporally regulated by the epigenome.
近年来，空间组学方法的发展使得能够以高空间分辨率对转录组和 3D 基因组结构进行单细胞分析。为了扩展空间组学工具的组合，一种空间分辨的单细胞表观基因组学方法将加速理解细胞和组织功能的空间调控。在这里，我们报告了一种使用原位标记和转录随后进行多重成像的单细胞表观基因组空间分析方法。我们证明了能够在单个细胞中分析标记活性启动子、假定增强子和沉默启动子的组蛋白修饰的能力，并生成了数百个胚胎和成年小鼠大脑中活性启动子和假定增强子的高分辨率空间图谱。我们的结果表明，假定的启动子-增强子对和调节发育重要基因的增强子枢纽。我们设想这种方法将普遍适用于表观遗传修饰和 DNA 结合蛋白的空间分析，从而增进我们对基因表达如何受到表观基因组的时空调控的理解。
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