Revealing novel molecular mechanisms linking DNA replication and cell fate decisions

Project Information

RepDiff

Grant agreement ID: 846375

DOI

10.3030/846375

Project closed

EC signature date 10 April 2019

Start date 1 January 2020

End date 31 December 2021

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 219 312,00

EU contribution

€ 219 312,00

Coordinated by

KOBENHAVNS UNIVERSITET
Denmark

Periodic Reporting for period 1 - RepDiff (Revealing novel molecular mechanisms linking DNA replication and cell fate decisions)

Reporting period: 2020-01-01 to 2021-12-31

Summary of the context and overall objectives of the project

During normal development our cells go through programmed changes in cell identity that alter their properties. In diseases like cancer, our cells undergo unscheduled changes in cell identity. Cell division play a major role in both processes. To divide, the genetic code must be copied to be transferred to both daughter cells, and this entails a transient disruption of the chromatin landscape that organises and regulates the genome. The window of chromatin replication may represent an important opportunity to facilitate chromatin reorganisation for cell reprogramming towards a different identity. In this project I sought to explore this hypothesis by identifying chromatin replication and restoration proteins which have a role in maintaining the pluripotent state and the engagement of mouse embryonic stem cells into differentiation. This insight will advance our understanding of mechanisms which take action in normal and abnormal cell fate transitions. This work, although not yet finalized, revealed novel link between chromatin replication and stem cell potency.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

I characterised chromatin replication proteins which play a role in stem cell plasticity. This work links chromatin replication and restoration, epigenetic inheritance and developmental competence of mouse stem cells. Publication of this work will provide a new understanding of cellular plasticity and open new research avenues in epigenetics and stem cell biology.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

This work provided new link between chromatin replication and restoration, epigenetic inheritance and mouse embryonic cellular plasticity. This work results could create new working model to delineate mechanisms which underpin abnormal cell fate transitions, as in cancer.

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