EpiNoise · The role of epigenetic heterogeneity in cell fate decisions
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-09-01 → 2022-03-01
- EU contribution
- €183,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
The role of epigenetic heterogeneity in cell fate decisions
Early mouse development is characterised by extensive remodelling of chromatin accessibility and DNA methylation (DNAme). These changes are essential for the establishment of the pluripotent state and for subsequent cell fate decisions. Mutants that fail to correctly remodel their accessibility or methylation landscapes display differentiation defects and often die before birth. But while it is clear that the correct establishment of chromatin accessibility and DNAme is essential for cell fate specification during development, the dynamic relationship between these two layers of regulation and their effects on gene expression over the course of development are largely unknown. This results from the fact that bulk methods for transcriptome, methylome and accessibility analysis provide population data and obscure relevant cellular heterogeneity which is abundant in the early embryo. The aim of this project was to uncover the roles of chromatin accessibility and DNA methylation in gene regulation and in cell fate specification during mouse development. This work may open up new avenues of applied research in amongst others regenerative medicine where the aim is to tightly control cell fate.
Data: CORDIS, © European Union
Project objective
A fundamental question in biology is how different cell fates are generated. While it is clear that extensive remodelling of chromatin accessibility and DNA methylation is an essential step in early mammalian development, their roles in cell fate specification remain unclear. Furthermore, it is not known to what extent cell-to-cell differences in gene expression regulation affect cell fate decisions. The aim of this proposal is to uncover the roles of chromatin accessibility and DNAme in gene regulation and in cell fate specification during mouse development. I will use a novel sequencing approach for combined profiling of chromatin accessibility, DNA methylation and transcription in single cells as well as other state-of-the-art technologies to provide unique insights in the connection between chromatin accessibility, DNAme and transcription at the single cell level. Moreover, this proposal has the potential to drastically change our view of germ layer specification by highlighting the role of cellular heterogeneity in this process. Together, this will improve our understanding of both pluripotency and differentiation, advancing the fields of stem cell research and development. The proposed research combines my experience in the areas of cellular heterogeneity and multidisciplinary science with the host’s experience in single cell genomics, epigenetics and mouse development. The knowledge and skills gained from this project combined with my scientific and personal development will prepare me for my goal of establishing my own academic research group.
Original text from CORDIS.
Participants
- THE BABRAHAM INSTITUTE · CambridgeCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union