Scientists at the Institute for Stem Cell Research, of the University of Edinburgh show that mouse embryonic stem cells need the protein FGF4 to become competent to be converted into specialized cell types, such as brain or muscle cells.

These findings add to the growing body of knowledge that researchers all over the world are using to direct embryonic stem cells to become specific specialised cells – a fundamental requirement for using lab-grown cells to model disease, test the effects of new drugs and, potentially, treat disease and injury.

Embryonic stem cells have the unique ability to divide to produce both copies of themselves and other, more specialised, cell types. The process whereby embryonic stem cells commit to become specialised cells is still obscure. In particular, the precise role of the protein Fibroblast Growth Factor 4 (FGF4) in this key decision point has been uncertain, until now.

Dr Tilo Kunath and Prof Austin Smith, together with collaborators in Montreal, Canada, show that FGF4 is not involved in the maintenance of cells in the naïve, self-renewing state but is essential to prime cells into a transitional stage, wherein they can go down any one of several paths.

Says Tilo, ‘Depending on the signal presented to the mouse embryonic stem cells, they can go back to the naïve state, and divide without limit, or down one of several specialisation pathways, including routes towards nerve cells or muscle cells. We have coined a name for the cells in this stage – we call them ‘commitment-competent’ cells, in contrast to the embryonic stem cells who do not receive a signal from FGF4, which we call ‘commitment-phobic’.

Human embryonic stem cells need FGF protein to grow in a dish. Whether this is required for maintenance of the human stem cells, or for priming the cells for specialisation, similarly to FGF4, is not yet known. If confirmed in human embryonic stem cells, these latest findings provide a further handle on how to manipulate these cells so as to direct them down specific pathways and obtain specialised cells.

This work was funded by a Parkinson’s Disease Society fellowship held by Tilo Kunath, with support from Stem Cell Sciences PLC, the Biotechnology and Biological Sciences Research Council (BBSRC), the Medical Research Council (MRC), the European Commission Integrated Project ‘EuroStemCell’, and the National Cancer Institute of Canada.