CBE/ENGR 225 Seminar Presents: Siddharth Dey, Ph.D., Assistant Professor, Dept. of Chemical Engineering, UCSB
Siddharth Dey, Ph.D.
Assistant Professor, Dept. of Chemical Engineering
University of California, Santa Barbara
Tuesday, April 4, 2017
ESB, Room #2001
*Cookies and Coffee will be provided*
Integrated Methylome and Transcriptome Sequencing of the Same Cell Enables Lineage Reconstruction and Reveals Two Distinct Modes of Global Demethylation Dynamics
A central question in biology is to understand how variability in the epigenome regulates gene expression heterogeneity and cell fate decisions. During early mouse embryogenesis, it is well-known that the first defined cell types – the trophectoderm and inner cell mass – are found at the blastocyst stage of development. There is increasing evidence that the totipotent cells that give rise to these well-defined cell types in the blastocyst show biased lineage potential early in development. What remains unclear is at exactly what stage of preimplantation development is lineage specification initiated and whether the totipotent cells divide symmetrically and/or asymmetrically to give rise to the blastocyst. In the first half of my talk, I will be discussing our attempts at addressing these questions by developing novel tools that allow endogenous lineage reconstruction (using the epigenetic mark 5-hydroxymethylcytosine, 5hmC) and mRNA quantification from single cells. At the molecular level, one of the most dramatic epigenetic changes that occur during preimplantation development is the global erasure of DNA methylation from the parental genomes. In the second half of my talk, I will be describing a new technology to quantify DNA methylation in single cells and how we are using it to probe the dynamics of demethylation. We are discovering that in contrast to previous studies that have suggested that maternal demethylation occurs primarily through the lack of methylation maintenance during replication (known as “passive” demethylation), our results suggest a more complex mechanism of demethylation that involves both passive and other enzymatic pathways (known as “active” demethylation). Thus, this talk will explore how new single-cell sequencing technologies are enabling us to study biological systems at a previously unexplored resolution.