Diverse cell types in tissues have distinct gene expression programs, chromatin states and nuclear architectures. To correlate such multimodal information across thousands of single cells in mouse brain tissue sections, we demonstrate integrated spatial genomics, imaging thousands of genomic loci along with RNAs and epigenetic markers simultaneously in individual cells. We revealed that cell type–specific association and scaffolding of DNA loci around nuclear bodies organize the nuclear architecture and correlate with differential expression levels in different cell types. At the submegabase level, active and inactive X chromosomes access similar domain structures in single cells despite distinct epigenetic and expression states. Our report represents a major step forward in linking single-cell 3D nuclear architecture, gene expression and epigenetic modifications in native tissue context.

中文翻译：

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小鼠大脑中跨细胞类型的单细胞核结构


组织中的不同细胞类型具有不同的基因表达程序、染色质状态和核结构。为了将小鼠脑组织切片中数千个单细胞的多模态信息关联起来，我们展示了集成的空间基因组学，在单个细胞中同时对数千个基因组位点以及 RNA 和表观遗传标记进行成像。我们揭示了细胞类型特异性关联和核体周围 DNA 位点的支架组织核结构，并与不同细胞类型的差异表达水平相关。在亚兆碱基水平上，尽管表观遗传和表达状态不同，但活性和非活性 X 染色体在单细胞中访问相似的结构域结构。我们的报告代表了在天然组织环境中将单细胞 3D 核结构、基因表达和表观遗传修饰联系起来的重大一步。