Profiling epigenetic modifications and lineage specifications using single-cell multi-omics

Abstract

Developmental biology studies the processes that take place when a fully formed organism arises from just one single cell. At the level of gene regulation, the correct genetic programs need to be switched on and alternative patterns need to be blocked. This is achieved by the placement of modifications on top of the DNA, termed epigenetic modifications. Recently developed techniques allow the read-out of these characteristics in single cells. Chapter 1 provides an overview of developmental biology and these techniques, and chapter 3 introduces a new method for profiling epigenetic modifications and the cell type in single cells. To study the development of organisms, in vitro systems that mimic aspects of embryogenesis have been developed. Chapter 2 investigates how these structures form, and proposes a more efficient and stable protocol. This protocol is applied in chapter 3, after which the epigenetic modifications of these in vitro systems are profiled. This shows a high degree of similarity between in vitro systems and in vivo embryonic development. In chapter 4, an attempt is made to reconstruct a lineage tree in these in vitro systems, to study which cell types share common ancestors. Chapter 5 places the research of this thesis in the context of embryonic development and technique development.