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Systems biology approaches to understand cell pluripotency Acronym: PluriSys

Periodic Report Summary - PLURISYS (Systems biology approaches to understand cell pluripotency Acronym: PluriSys)

Project objectives:

The PLURISYS project is aimed at increasing the fundamental knowledge of basic biological processes of cell pluripotency and differentiation by generating new holistic data on gene expression and epigenetic modifications associated with cell pluripotency. The project integrates the multidisciplinary excellence in Europe in cell biology, molecular biology and bioinformatics. It also builds on earlier efforts, as consortium partners are leading partners in several European Union (EU) funded projects in these areas. The PLURISYS project links for the first time research activities in different mammalian systems, including murine, porcine and bovine, and in different cell types, from pluripotent cells in pre-implantation embryos, through embryonic stem cells, to epiblast-derived stem cells. Novel bioinformatics approaches and tools will be developed to set common standards for data analyses among all consortium members and, at a wider scale, to provide an integrated data base matching the requirements of systems biologists. Training, education and outreach activities are structured to assure the maximum efficiency in developing and spreading the new standards and to increase the impact of the project for the European health sector. The project integrates small and medium-sized enterprise (SME) partners and academic institutions from seven countries from all regions of the EU and will help to decrease the fragmentation of ERA. The main impact of the project is expected as integrating efforts in cell biology, cell therapy, molecular biology and bioinformatics for future applications of systems biology on the relevant questions of cell pluripotency and differentiation. Furthermore, the project is expected to yield pracically useful results, such as improved procedures for the derivation, maintenance and differentiation of pluripotent stem cell lines in mouse and large animals, with potential future applications in the fields of regenerative medicine and tissue engineering, and, beyond these areas, in pharmaceutical industry and agriculture.

The main objective of the PLURISYS is to make significant advances in the questions of genetic and epigenetic regulation of pluripotency and differentiation and provide a fuller characterisation of the gene regulatory and epigenetic modifications that occur, to in turn understand its implications on the programme of gene expression found in different stem cell types from different mammalian species. The approach focuses on the use of high throughput enabling technologies on predominantly primary and established mouse, bovine, porcine and human ESC, TS and EpiSC lines. Increasing the output of research and expanding the comparative knowledge of gene regulatory systems will make results more amenable to therapeutic and diagnostic applications for health, and hence to clinical trials and commercial exploitability.

The impact of the project is very broad. Stem cell research offers a great promise for cell therapy by generating cells, tissues and eventually organs for medical purposes. Furthermore, in animals, embryonic stem cell based methods are used for the generation of transgenic animals, used as medical models, bioreactors and for agricultural production. Stem cell culture establishment, maintenance and differentiation methods are developing quickly. Despite the great progress on methods and increase in knowledge on stem cell physiology and the key factors for 'stemness', there are many fundamental issues still to be clarified.

Beyond the direct goals of PLURISYS project, there are potential benefits of generating additional knowledge on large animal stem cells, and potentially immortal embryonic stem cell (ESC) or epiblast stem cell (EpiSC) lines. In spite of the fact that nuclear transfer has become the method of choice for production of genetically modified pigs and bovine, pluripotent stem cell lines may still offer certain advantages in these species.