MeGa · DNA Methylation dynamics during Gastrulation
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-09-01 → 2021-04-03
- EU contribution
- €195,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
DNA Methylation dynamics during Gastrulation
The embryo development is a complex process in which a single totipotent cell generates a multicellular organism. During this process, hundreds of different cell types differentiate and acquire their own identity. This is orchestrated by large-scale changes in gene expression programs and a drastic remodeling of the epigenome. Epigenetic changes allow to activate the correct genes at the precise developmental stages at the same time they stabilize differentiated states once cell fate is specified. In mammals, studying how these changes occur is particularly challenging due to internal gestation and the complexity of developmental pathways. In addition, the static nature of sequencing technologies only allows the study of a developmental snapshot in time, substantially limiting the understanding of cell fate trajectories. Using the mouse as a model, this project investigates the links between the epigenome and transcriptome during early development from a novel and unique temporal perspective. For this purpose, we have developed a novel single cell multiomic technology which records cell lineage relationships. The obtained information is used to monitor and understand the propagation of key developmental cell decisions throughout cell generations. This project also explores how DNA methylation marks contribute to lock in differentiated states preventing a return to less specialized fates. This is particularly important for stem cell therapies as failure to acquire these marks affects long-term cellular stability. The results of this project will also provide fundamental insights into the field of epigenetics, mammalian development and stem cell biology.
Data: CORDIS, © European Union
Project objective
A fundamental aspect of biology is the understanding of how cell fates are established and maintained. Although it is widely accepted that epigenetic reprogramming is a central process of mammalian development, one of the most intriguing questions that remains unanswered is how DNA methylation marks contribute to cell differentiation and lineage commitment. By combining, novel single cell genomics techniques, CRISPR/dCas9 technology and innovative analytical approaches, this project will uncover the links between DNA methylation, gene expression and cell fate decisions during mouse gastrulation. This information will be used in a novel way to identify methylation signatures responsible for the stable repression of pluripotency, which has great potential to advance the development of safe iPS cells. Furthermore, this proposal will implement two innovative approaches utilising single cell DNA methylation patterns to reconstruct lineage trajectories of individual cells. This project capitalises on the unique combination of my novel analytical approaches, my background in DNA methylation analysis and evolutionary biology together with the extensive expertise in single cell techniques and developmental biology of the host lab. This multidisciplinary proposal will provide critical insights into how information is encoded in the epigenome and what this information can tell us about a cell’s history within a developing organism. These results will significantly advance the field of epigenetics, developmental and stem cell biology. Finally, the knowledge and skills gained from this project combined with my scientific and personal development will hopefully open up exciting career possibilities with the long-term goal to establish my own research group in Europe.
Original text from CORDIS.
Participants
- THE BABRAHAM INSTITUTE · CambridgeCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union