Skip to main content

Learning from the past: linking ancestral epigenetic states to current cellular fates with single-cell multi-omic approaches

Objective

The establishment of cell type-specific transcriptional programs involves many interconnected regulatory mechanisms acting on different genomic scales. To dissect this multi-layered control of gene expression in detail, I will develop methods that a) measure multiple cellular outputs in single cells, and b) obtain that information in a time-resolved manner. This proposal outlines my approach to study early mouse development at numerous levels, including (but not limited to) transcription, chromatin context, and nuclear organization. In doing so, I expect to shed light on the mechanism behind cell fate specification and the epigenetic states that precede it.

I will develop a novel strategy to simultaneously profile many factors involved in gene regulation in the same cell. Its successful implementation will give insight into transcriptional control at unprecedented modality, revealing the causal relationships between histone modifications, spatial positioning within the nucleus, Polycomb group proteins, and others. Next, I will pursue several “molecular memory” strategies to obtain recordings of past regulatory states, followed by multi-omic readouts at later developmental times. Such retrospective analyses enable linking fate decisions to past molecular events in the same cell, thereby permitting careful reconstruction of the molecular trajectories underlying cell fate choice. Finally, these and previously developed single-cell methods will be applied to unravel the gene-regulatory mechanisms that govern lineage determination in early mouse development.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/epigenetics

Call for proposal

ERC-2020-COG
See other projects for this call

Funding Scheme

ERC-COG - Consolidator Grant

Host institution

KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
Address
Kloveniersburgwal 29 Het Trippenhuis
1011 JV Amsterdam
Netherlands
Activity type
Other
EU contribution
€ 2 000 000

Beneficiaries (1)

KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
Netherlands
EU contribution
€ 2 000 000
Address
Kloveniersburgwal 29 Het Trippenhuis
1011 JV Amsterdam
Activity type
Other