CORDIS - EU research results

Functional Genomics in Engineered ES cells

Final Report Summary - FUNGENES (Functional Genomics in Engineered ES cells)

The FUNGENES project aimed to achieve a detailed basic understanding of stem cell self-renewal and differentiation. It thoroughly investigated the unique ability of mouse embryonic stem cells to develop into cells of any organ ("pluripotency"), created new tools for functional genomic studies and thus provided key knowledge to understanding the commitment of cells to differentiate into cells of a particular germ layer. This complex process occurs in several steps and controls the development of pluripotent cells into highly specialised cells of an organism.

In particular, FUNGENES identified genes controlling the development of pluripotent embryonic stem (ES) cells into heart cells (cardiomyocytes), nerve cells (neurons), smooth muscle cells, vascular endothelial cells, fat cells (adipocytes), liver cells (hepatocytes) and insulin-producing cells of the pancreas.

FUNGENES identified the gene subsets that are active in self-renewing cells, during the exit from pluripotency and at specific stages of mouse ES cell differentiation. Its major objective was to produce a gene expression atlas covering the development of ES cells into all three germ layers (ecto-, meso-, and endoderm) and into somatic cells. Understanding the genetic pathways underlying differentiation of ES cells to somatic cells would contribute to future therapeutic strategies for degenerative diseases such as heart disease, diabetes and Parkinson's. All these diseases are characterised by the irreversible loss of functional cells.

More specifically, the consortium:
1. developed a detailed understanding of embryonic stem cell self-renewal, differentiation and lineage commitment to different organ-specific cells, including the identification of potential novel target genes for therapeutic intervention;
2. derived new cellular and molecular tools to characterise gene function in tissue-specific cell populations (functional genomics);
3. developed new embryonic stem cell-based approaches to screening of small candidate molecules for therapeutic applications in human diseases.