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Nuclear foundations of cellular potency

Objective

A fundamental question in biology is to understand the mechanisms underlying cell plasticity. Such plasticity or potency is essential to form multiple cell types upon differentiation. In mammals, upon fertilization and fusion of the gametes –two highly differentiated cells- intense chromatin remodeling and epigenetic reprogramming, the reversion into an undifferentiated state, are essential to restore full developmental potency (totipotency). Subsequent development and differentiation are accompanied with progressive loss of plasticity. The transition between totipotency and the gradual loss of plasticity is thought to be regulated by yet-unknown epigenetic mechanisms.

The embryonic chromatin displays unique features compared to differentiated cells, including the lack of ‘conventional’ heterochromatin. We hypothesise that the transition from a totipotent state to a differentiated one is regulated by changes in chromatin states, particularly by de novo acquisition of heterochromatin domains.

This project is designed to reveal the nuclear foundations of totipotency by determining the molecular mechanisms underlying the establishment of heterochromatin and their functional role in maintaining totipotency using the mouse embryo as model.

We will do this by:
i)determining the functional relationship of heterochromatin and nuclear architecture
ii)by determining the effects of artificially inducing heterochromatin on cell potency during development and
iii)by determining the mechanisms that regulate heterochromatin formation in the embryo.

We anticipate that our studies will unravel fundamental mechanims on how chromatin states regulate cell potency during reprogramming. By uncovering such mechanisms, we expect to reveal new insights that will be useful to induce epigenetic reprogramming of differentiated cells. Our results will therefore lead to key contributions in the fields of stem cell, developmental biology, human reproduction, chromatin biology and epigenetics.

Field of science

  • /medical and health sciences/medical biotechnology/cells technologies/stem cells
  • /natural sciences/biological sciences/developmental biology
  • /natural sciences/biological sciences/genetics and heredity/epigenetics
  • /medical and health sciences/clinical medicine/embryology

Call for proposal

ERC-2011-StG_20101109
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Address
Ingolstadter Landstrasse 1
85764 Neuherberg
Germany
Activity type
Research Organisations
EU contribution
€ 542 185,62
Principal investigator
Maria-Elena Torres-Padilla (Dr.)
Administrative Contact
Jürgen Ertel (Dr.)

Beneficiaries (2)

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Germany
EU contribution
€ 542 185,62
Address
Ingolstadter Landstrasse 1
85764 Neuherberg
Activity type
Research Organisations
Principal investigator
Maria-Elena Torres-Padilla (Dr.)
Administrative Contact
Jürgen Ertel (Dr.)
CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE

Participation ended

France
EU contribution
€ 953 814,38
Address
Rue Laurent Fries 1
67404 Illkirch Graffenstaden
Activity type
Research Organisations
Administrative Contact
Steve Brooks (Dr.)