ESTOOLS - Advances with human embryonic stem cells - The ESTOOLS research programme

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The ESTOOLS research programme

Research objectives

Human embryonic stem (ES) cells have the potential to generate every cell type in the body, and so present exciting opportunities for the study of embryonic development and disease. They may also provide a new resource for the testing and screening of medical treatments, and eventually for transplantation in disease and injury where cells are lost or damaged.

For human ES cells to be used in this way, researchers must first be able to:

1. Expand stem cells indefinitely in the laboratory, without compromising their genetic or epigenetic identity.
2. Direct their differentiation into pure populations of specialised cell types.

Research workpackages

The ESTOOLS research programme is made up of nine workpackages.  eight are scientific in scope and directly address the above two key requirements. The ninth (WP6) considers ethical implications of this research – just as important when considering future biomedical applications of human ES cell research.

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click to jump to a visualisation of Workpackage connections

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Workpackage 1A - Leader: Outi Hovatta

Development and optimisation of standard culture conditions for human ES cells

This workpackage will develop and optimize standard conditions for the growth and expansion of human ES cells in the laboratory.  It aims to develop an automated cell culture system, and eliminate the use of feeder cells and animal substances – an important consideration if cells are to be transplanted in patients.  

 

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Workpackage 1B - Leader: Tariq Enver

Self renewal of human ES cells

This workpackage will identify and characterise the mechanisms that regulate the self renewal of human ES cells and their commitment to differentiation.

 

 

 

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Workpackage 1C - Leader: Nissim Benvenisty

The genetic stability of human ES cells

This workpackage will investigate the genetic changes that occur during the culture of human ES cells, the mechanisms that drive these changes and the effect of culture conditions upon the appearance of genetic variants.

 

 

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Workpackage 2 - Leader: Maarten van Lohuizen

Profiling of epigenetic regulation in human ES cell lines – influences on stability, self-renewal and lineage commitment.

This workpackage will study and map the role of epigenetic gene regulation in stability, self-renewal and differentiation of hES cells.  Relevant epigenetic regulators will be fully characterized. 

 

 

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Workpackage 3 - Leader: Andrew JH Smith

Recombination tools and genetic switches

This workpackage will investigate and develop advanced methodologies and tools for the genetic manipulation of human ES cells, including homologous recombination, RNAi, conditional mutagenesis, enhancement of lineage selection and RMCE. 

 

 

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Workpackage 4 - Leader: Meng Li

Characterisation and control of neural lineage commitment

This workpackage will develop an in-depth understanding of the mechanisms that control the commitment of human ES cells to the neural lineage.  It will define the requirements for reliable generation and purification of pan-neural precursors, and of more specialized neuronal- and glial-restricted progenitor cells with distinct regional specification. Our findings will then serve as a paradigm for future studies of other differentiation pathways.

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Workpackage 5 - Leader: Yves Barde

Generating and characterizing differentiated neurons and glial cells using human ES cells

This workpackage will test the possibility that human ES cells can be induced to generate specific populations of cells of the brain and nervous system.  It aims to define the requirements for the generation of these specialized cell types (neuronal sub-types, astrocytes and oligodendrocytes), paving the way for their use in modelling diseases of the nervous system 

 

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Workpackage 6 - Leader: Goran Hermeren

Ethical issues relating to basic human ES cell research

This workpackage will investigate and clarify the ethical issues raised by human ES cell research. It will address the ethical standards acceptable and required throughout the European Research Area for research with human ES cells and for the commercial exploitation of that research. More information about the ethics workpackage.

 

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Workpackage 7 - Leader: Oliver Bruestle

Induced pluripotent stem cells

This workpackage initiates development of a platform for robust conversion of human somatic cells into pluripotent stem cells that will enhance our understanding of the pluripotent state.

 

   

 

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To explore visually the key connections between workpackages 1-6, click the image.

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