Epigenomic Profiling With Ultralow-Input Microfluidic Assays: Technology, Biology, and Medicine

Abstract

Epigenome dictates turning on and off genes during normal development and diseases, forming another layer of regulation on top of gene sequence. Epigenome is cell-type-specific and highly dynamic over the course of disease and treatment thus offers a treasure trove of information for precision medicine. However, there is a giant gap between the number of cells that can be derived from patient samples and millions of cells per assay required by conventional epigenomic assays. In this seminar, I will discuss the role of microfluidics in conducting genome-wide epigenetic analysis using scarce samples derived from mice and patients. I will argue that microfluidics uniquely facilitates multi-step molecular biology manipulation required by epigenomic assays and interface between the assays and next-generation sequencing. I will describe the microfluidic technologies developed in my lab for profiling histone modifications and DNA methylation. These technologies work in the 30-200 cells per assay range and offer data quality comparable to those of conventional assays that require millions of cells. I will also discuss the biological insights we generated into cancer development and brain functions.