High-throughput Single Cell Co-assay of Histone Modifications and Transcriptome

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Abstract Epigenome analysis can help dissect the transcriptional regulatory sequences that control spatiotemporal patterns of gene expression during anima development and disease pathogenesis, but a major challenge to epigenome analysis is the heterogeneity of primary tissues. Conventional epigenome assays that take bulk tissues as input only produce population average signals. To address this major bottleneck, we propose to develop an ultra-high throughput single-cell multi-omics method, Paired-Tag, for joint profiling of histone modifications and transcriptome. In preliminary experiments, we have demonstrated the feasibility and utility of this method through analysis of the nuclear transcriptome and multiple histone modifications at single cell resolution in the adult mouse frontal cortex and hippocampus. In the proposed study, we will further optimize the current Paired-Tag protocol and demonstrate its utility in cancer epigenome analysis. If successful, the research would add a major toolkit for the production of cell-type-resolved maps of chromatin state and transcriptome in complex tissues and enable next generation epigenome analysis of tumor samples.