(190ax) Integrated Epigenome and Transcriptome Sequencing from the Same Cell

Biological systems are heterogeneous in nature and in the last five years single-cell genomics has revolutionized our understanding of such systems on a genome-wide scale. In particular, single-cell mRNA sequencing has identified dramatic cellular variability within tissues and tumor populations. However, it remains unclear how upstream epigenetic mechanisms regulate cell-to-cell heterogeneity in gene expression. Recent advances have enabled quantification of certain epigenetic marks at the single-cell level; however, to unambiguously understand how the epigenome regulates gene expression will require combined measurements of both quantities from the same cell. Therefore, we have been developing novel single-cell multiomics technologies to simultaneously detect epigenetic marks and mRNA from the same cell.

Gene expression is tightly regulated at many levels to ensure precise coordination of cell-type specific programs. For example, chemical modifications of DNA, chromatin mediated accessibility of DNA to transcription factors, and the 3-D organization of chromosomes in the nucleus of a cell play a critical role in regulating gene expression. Here, we present a new modular technology to simultaneously quantify the epigenetic features DNA methylation, DNA accessibility, or genome organization together with the transcriptome from the same cell. We use these technologies to study how these epigenetic features tune gene expression in mouse embryonic stem cells and their role in regulating the development of preimplantation mouse embryos.