Principle Investigator: Yaping Liu, PhD
Understanding the gene-regulatory circuits between genome, epigenome, and transcriptome, especially in the early developmental stage, requires simultaneous profiling of multiple molecular layers and their spatial organization in the same cell. Lack of such a genome-wide, single-cell resolution method, however, is a major hurdle.
We will develop a combined computational and experimental genome-wide assay to simultaneously profile the genetic variants, DNA methylation, DNA accessibility/nucleosome positioning, and chromosome conformation changes, which will allow us to phase the whole genome and multiple epigenomes in the same allele across the whole chromosome by a single bulk sequencing. Further, we are going to extract DNA and RNA separately to obtain additional transcriptome information and extend this technology to the single-cell resolution.
Finally, we will apply this novel single-cell, multi-omics approach to trace the developmental lineage commitment at a small scale during the retinoic acid (RA) induced differentiation of mouse embryonic stem cell (mESC). This technology will eventually allow us to simultaneously profile the genome, multiple layers of epigenome, 3D genome, and transcriptome together within the same single cell.